To see the other types of publications on this topic, follow the link: Naphthoquinone.
Dissertations / Theses on the topic 'Naphthoquinone'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Naphthoquinone.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Jones, Karen. "The basis for naphthoquinone and biguanide synergy." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368631.
Full text
2
Musa, Yusuf. "Studies of 1,2-naphthoquinone mono-oximato complexes." Thesis, London Metropolitan University, 1991. http://repository.londonmet.ac.uk/3286/.
Full textAbstract:
The synthesis of 1,2-naphthoquinone I-oxime and 1,2- naphthoquinone 2-oxina complexes of rhodium and Iridium has been Investigated. In the case of rhodium, complexes of the type Rh(l-nqo)3 have been prepared by reacting 1 ,2-naphthoquinone 1-oxime with hydrated rhodium(III) chloride. Both products ware obtained as mixtures of isomers. The Interaction of 1,2- naphthoquinone 2-oxime with rhodium(lll) chloride yielded Rh(2-nqo)3 also as a mixture of Isomers. The trichelates were also obtained from the nitrosation of the appropriate naphthol in the presence of rhodium(Ill) chloride. In contrast, the corresponding reaction systems involving iridium gave very complex mixtures Involving both iridium containing species and organic products. One of the iridium products, [pyH][lr(1-nqo)C13 pyl, has been isolated in the pure state and characterised by X-ray crystallography. The complexes Ir(1-nqo)3 and lr(2-nqo)3 were also isolated but in low yields. All trichelates ware shown to be diagmagnetic. None reacted with either pyridine or triphenylphosphine. These observations have been rationalised in terms of crystal field stabilisation energy. The behaviour of the rhodium and iridium complexes towards the Lewis bases contrasts that of analogous iron and cobalt complexes. The X-ray study of [pyH][lr(l-nqo)C13 py] has shown that the ligand is chelated to the metal as been observed in first transition series metal complexes derived from such ligands. The use of 1,2-naphthoqulnone 1-oxime as a potential ligand for separating rhodium from iridium has been investigated. Optimum conditions for recovery of rhodium was established, as a technique for refining rhodium current process at Inco (Europe) Ltd. The synthesis of cobalt, rhodium, copper, iron and nickel complexes of 1 ,2-naphthoquinone l-oxime-3,6- disulphonic acid (nRsH3) has been investigated and the complexes were isolated in solid form by developing a separation technique. Cobalt(III) and rhodium(III) salts reacted with the ligand to give metal complexes of type M(nRs Na)3 . The behaviour of the 1,2-naphthoquinone 1- oxime-3,6-disulphonic acid towards iron(ll) and iron(lll) or copper salts was shown to be more complex and interesting than previously reported. Both iron(II) and iron(III) chloride gave an Iron(II) product of the type Fe(nRs Na) whilst Iron(II) ammonium sulphate gave an Fe(II) product of the type Fe(nRs Na)2. The nickel salts gave a complex containing two ligands per metal, Ni(nRsHNa)2. The complexes of Iron(II) and copper(Il) of 1 ,2-naphthoquinone l-oxime-3,6-disulphonic acid catalysed aerobic oxidation of catechols. The oxidation involved oxidative cleavage of the aromatic ring of catechol by molecular oxygen to give muconic acid anhydride and 2H-pyran-2-one in addition to benzoquinone. This behaviour is very similar to enzyme catalysed oxygenation.
3
Stoten, William C. "1,2-naphthoquinone mono-oximato complexes of ruthenium." Thesis, London Metropolitan University, 1988. http://repository.londonmet.ac.uk/3429/.
Full textAbstract:
The ruthenium(II) complexes Ru(nqo)2 (nqoH = 1,2-naphthoqulnona 1-oxima, or 2-oxima) were prepared by the interaction of the sodium salts of the 112-naphthoquinone mono-oximes with hydrated ruthenium(III) chloride in aqueous tetrahydrofuran.
4
Fisher, Kimberly D. "Thermal rearrangement of 4-aryl-4-hydroxy-2-cyclobuten-1-ones and application of the methodology in the formation of benzofuronaphthoquinones and benzocarbazolequinones." Morgantown, W. Va. : [West Virginia University Libraries], 2008. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5872.
Full textAbstract:
Thesis (Ph. D.)--West Virginia University, 2008.Title from document title page. Document formatted into pages; contains xvi, 200 p. : ill. Includes abstract. Includes bibliographical references (p. 95-97).
5
De, Koning Charles Bernard. "The syntheses of some naturally derived naphthoquinones." Doctoral thesis, University of Cape Town, 1987. http://hdl.handle.net/11427/22000.
Full textAbstract:
Bibliography: pages 193-195.The synthesis of the naphthalene core of the ansamycin antibiotics, 8-acetyl-3-acetylamino-5,7-dihydroxy-1,4-naphthoquinone from benzoquinone by means of simple reactions including, Diels-Alder adduct formation, mild acetylation, oxime formation and Beckmann rearrangement in five steps with an overall yield of 22% is described in Chapter 1. The synthesis of the naturally occurring naphthoquinone derivative, possessing anti tumour and antiprotozoal properties, bikaverin is described in Chapter 2. Starting from vanillin the key intermediate 2-(2'-benzyloxy-6'-methyl-4'-methoxybenzoyl)-1,4,5,6,8-pentamethoxynaphthalene was prepared in six simple steps in an overall yield of 18%. This key intermediate was converted into bikaverin utilizing two independent routes. In the first route the benzyl group was removed from the key intermediate by hydrogenolysis followed by oxidative spiro ring formation , with 2,3-dichloro-5,6-dicyanobenzoquinone. After effecting xanthone ring formation and removal of two methyl groups with lithium iodide, bikaverin was produced in six steps in an overall yield of 32%. In the second route the key intermediate was first oxidised by silver (II) oxide this was followed by removal of the benzyl group and two methyl groups peri- to the quinone with boron trichloride, which led to spontaneous spiro ring formation, ultimately bikaverin was produced in three steps in an overall of 34%. The syntheses of the naturally occurring product ventiloquinone E and its trans-isomer as well as an isomer of the naturally occurring ventiloquinone J and its trans-isomer are described in Chapter 3. Starting from 1,2,4,5,8-pentamethoxynaphthalene, the synthesis of which has been described in Chapter 2, ventiloquinone E was prepared in nine steps in an overall yield of 7%. Similarly an isomer of ventiloquinone J was also prepared from 1,2,4,5,8-pentamethoxynaphthalene in ten steps in an overall yield of 6%. In both cases a mixture of cis-and trans-isomers was obtained, a successful resolution of both mixtures was accomplished by thin layer chromatography. By two other methods the trans-isomer of ventiloquinone E could be prepared in either nine steps in an overall yield of 23% or in six steps with an overall yield of 30% starting from the same pentamethoxynaphthalene.
6
Song, Ronghui. "Synthesis, Characterization and Antimicrobial Properties of Novel Naphthoquinone Derivatives." Kent State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1586783242508385.
Full text
7
Bapela, Mahwahwatse Johanna. "Variation of active constituents in Euclea natalensis based on seedling stages, seasons, and fertilizers." Pretoria : [s.n.], 2007. http://upetd.up.ac.za/thesis/available/etd-06262008-095522/.
Full text
8
Brenstrum, Timothy James. "Studies towards the synthesis of medermycin." Phd thesis, Department of Organic Chemistry, 1999. http://hdl.handle.net/2123/8846.
Full text
9
Yatchang, Marina Fosso. "Synthesis and Biological Activity of Aminoglycosides and 1,4-Naphthoquinone Derivatives." DigitalCommons@USU, 2012. https://digitalcommons.usu.edu/etd/1371.
Full textAbstract:
The research described in this dissertation is at the interface of organic chemistry and biology, and it aimed at designing and synthesizing biologically active molecules for the possible development of therapeutic agents. Spinal muscular atrophy is an incurable disease that affects 1 in every 6000 babies, making it the leading genetic cause of infant mortality. While no treatment is available, efforts are being taken to solve this issue. Part of the work outlined in this dissertation was carried out in collaboration with researchers from the University of Missouri to investigate a potential therapeutic for this disease. In addition, the continuous outbreak of diseases caused by bacteria demands for new and improved antibiotics that could help eradicate those pathogens. My research thus allowed me to discover molecules with interesting activity against bacteria for the possible development of potential antibacterial agents. Finally, my research also allowed me to develop potential agro fungicides, which are still very much needed nowadays. Many crop diseases are due to fungal infections,which globally cause enormous economic losses. The use of fungicides is still the main strategy to control these diseases. However, current agro fungicides show some limitations. This is illustrated with Fusarium head blight (FHB), a destructive and costly disease of wheat, barley and other small grains, whose economic losses in the Central United States alone were estimated to $2.7 billion.
10
Mahmood, Tariq. "Aspects of the chemistry of 1,4-naphthoquinones : an investigation of nucleophilic substitution reactions of alkylamines and hydroxyalyklamines on 1,4 napthoquinones and the role of solvent on the position of substitution." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5746.
Full textAbstract:
Nucleophilic substitution reactions of alkylamines, cyclic alkylamines, and hydroxyalkylamines with 5-substituted-1,4-naphthoquinones have been studied. It has been found that the nature of the solvent employed in the reaction influences the position of mono-substitution at either the 2- or 3-position. Although both regioisomers were produced in all the reactions, protic polar solvents favoured the formation of the 3-regioisomer, whereas non-protic solvents favoured the formation of the 2-regioisomer. It has also been found that formation of 2,3-diaminoalkyl derivatives is normally unlikely. A series of hydroxyalkylamino-1,4-naphthoquinones were also synthesised. The collision-induced dissociation mass spectra of protonated hydroxyalkylamino-1,4- naphthoquinones showed fragmentation patterns which were dependent on the nature and length of the side chain and the presence and nature of the adjacent group on the 3-position on the 1,4-naphthoquinone ring. A total of 27 novel compounds were synthesised during the course of this research, the structures of which were confirmed via 1D and 2D NMR spectroscopy, mass spectrometry (ESI), IR spectroscopy and high resolution mass spectrometry (HRESIMS and HREIMS).
11
劉曉霞 and Xiaoxia Liu. "Coordination Chemistry of 1,2-naphthoquinone-mono-oxime withruthenium, rhodium and palladium." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B3124063X.
Full text
12
Liu, Xiaoxia. "Coordination Chemistry of 1,2-naphthoquinone-mono-oxime with ruthenium, rhodium and palladium /." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2168781X.
Full text
13
Sardhalia, Vaskar. "Calcium carbonate-naphthoquinone hybrid pigments inspired by biomineral coloration in sea urchins." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS644.pdf.
Full textAbstract:
Les couleurs vives observées dans les biominéraux provenant d'oursins adultes, allant du violet au vert, sont attribuées à la présence de molécules de naphtoquinone polyhydroxylée (PHNQs). Ces PHNQs sont intégrés dans la calcite, probablement au cours de la croissance cristalline, se produisant via l'intermédiaire de précurseurs de carbonate de calcium amorphe (ACC). La formation de minéraux chez les oursins s'accompagne de changements de couleur dépendant du stade de minéralisation. Le spinochrome A, par exemple, présente une couleur rouge lorsqu'il est extrait des épines violettes de Paracentrotus lividus en conditions acides, ce qui indique un lien potentiel entre le pH et les variations de couleur telles qu'observées dans la formation de CaCO3. Pour avoir une meilleure compréhension de ces variations de couleur et de l'impact des naphtoquinones sur la cristallisation de l'ACC, nous avons effectué une précipitation de CaCO3 en présence de PHNQs (extraits d'épines d'oursins) et de naphtoquinones naturelles disponibles dans le commerce (naphthazarine, lawsone et juglone). Nous avons contrôlé le pH tout au long de la formation de l'ACC coloré et de sa cristallisation en calcite. Différentes techniques analytiques, dont la DSC/ATG, l’XPS, l’analyse PDF, la spectroscopie UV-Vis, le STEM-EELS, la spectroscopie RMN en phase solide et la DRX HR, ont été utilisées pour caractériser les propriétés des pigments hybrides amorphes et cristallins. Nos résultats révèlent que différents pigments peuvent créer un spectre de calcite colorée. Par exemple, la naphtazarine, rouge à un pH acide, puis bleue avant la précipitation de l'ACC, donne finalement une calcite bleue lavande, en raison d’une déprotonation/protonation successive des OH. L'effet de l'augmentation de la concentration de naphtaline sur la stabilité de l'ACC face à la cristallisation en solution et à l'air suit des tendances différentes sans affecter la structure locale de l'ACC. La quantification de la naphtaline associée à l'ACC et à la calcite révèle que seule une infime partie de la naphtaline associée à l'ACC est incorporée dans la calcite, et ce sous la forme de nano-inclusions non homogènes ; tandis que le reste est adsorbé à la surface sous l'effet de fortes forces chimiques ou physiques. En outre, le spinochrome A conduit à l’obtention de calcite violette, tandis que les spinochromes B et E à de la calcite jaunâtre. L'analyse DRX HR indique que les spinochromes B et E induisent des distorsions plus importantes dans le réseau de la calcite que le spinochrome A. De plus, le spinochrome A augmente la stabilité du polymorphe intermédiaire, modifiant ainsi la voie de cristallisation. La combinaison d'effets structurels atomiques minimes et d'une coloration intense suggère une incorporation préférentielle du spinochrome A dans les épines pourpres de P. lividus. Les PHNQs extraits des épines d'oursins et les pigments hybrides ont été testés pour la teinture des textiles, montrant des résultats prometteurs dans le cas des PHNQs biogéniques et des pigments hybrides à base d'ACCThe vibrant colors seen in adult sea urchin biominerals, ranging from purple to green, are attributed to the presence of polyhydroxylated naphthoquinone molecules (PHNQs). These PHNQs become integrated into calcite, likely during the crystal growth, which occurs through amorphous calcium carbonate (ACC) precursors. The mineral formation in sea urchins is accompanied by color changes depending upon the stage of mineralization. Spinochrome A, for example, exhibits a red color when extracted from the purple spines of Paracentrotus lividus in acidic conditions, indicating a potential link between pH and color variations, as observed in CaCO3 formation. To delve deeper into color variations and the impact of naphthoquinones on ACC crystallization, we performed CaCO3 precipitation in the presence of PHNQs (extracted from sea urchin spines) and commercially available natural naphthoquinones (naphthazarin, lawsone, and juglone). We monitored pH levels throughout the formation of colored ACC and its crystallization into calcite. Various analytical techniques, including DSC/TGA, XPS, PDF analysis, UV-Vis, STEM-EELS, ss-NMR spectroscopy, and HR-XRD, were employed to characterize the properties of the amorphous and crystalline hybrid pigments. Our results reveal that different pigments can create a spectrum of colored calcite. For instance, naphthazarin, transitioning from red at acidic pH, turns medium blue before ACC precipitation, culminating in lavender blue calcite due to successive O-H deprotonation/protonation. The effect of increasing naphthazarin concentration on ACC's stability against crystallization in solution and air followed different trends without affecting the local structure of the ACC. Quantification of naphthazarin associated with ACC and calcite revealed that only a tiny fraction of naphthazarin associated with ACC gets incorporated within the calcite in the form of non-homogeneous nano inclusions; the rest was adsorbed on the surface with strong chemical or physical forces. Furthermore, spinochrome A yields purple calcite, while spinochrome B and E produce yellowish calcite. HR-XRD analysis indicates that spinochrome B and E induce more significant distortions in calcite lattice than spinochrome A. Moreover, spinochrome A increased the stability of the intermediate polymorph, thus modifying the crystallization pathway. The combination of minimal atomic structural effects and intense coloring suggests a preference for incorporating spinochrome A in the purple spines of P. lividus. The PHNQs extracted from sea urchin spines and hybrid pigment were tested for textile dyeing, showcasing promising results in the case of biogenic PHNQs and ACC-based hybrid pigments
14
García-Martínez, Israel. "Microwave assisted solid-supported organic systhesis a novel development of a methodology to obtain 2,3-disubstituted-1,4-naphthoquinones /." To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2009. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Full text
15
McManus, Joshua David. "A search for shorter, more convergent routes to enantiopure naphthopyrans related to the aphid insect pigments." Thesis, McManus, Joshua David (2007) A search for shorter, more convergent routes to enantiopure naphthopyrans related to the aphid insect pigments. PhD thesis, Murdoch University, 2007. https://researchrepository.murdoch.edu.au/id/eprint/695/.
Full textAbstract:
The naphtho[2,3-c]pyran ring system is generally found amongst natural products as the 5,10- or 6,9-quinones. These compounds display a wide range of biological activities, and as such, have been synthesised by various research groups. The synthetic work described in this thesis is directed towards finding shorter, more convergent routes to enantiopure quinone A 10, quinone A' 11 and quinone-pm 13, three derivatives of the aphid insect pigments protoaphin-fb 6, protoaphin-sl 7 and protoaphin-pm 9, respectively.
The first chapter describes the previous syntheses of some naphtho[2,3-c]pyrans including those relating to the aphid insect pigment derivatives. Also detailed is the ability of these naphthopyranquinones to act as potential bioreductive alkylating and dialkylating agents. The latter part of the chapter records some of the previously achieved assemblies of quinones A 10 and A' 11 in both racemic and enantiopure form, as well as the only synthesis of enantiopure quinone-pm 13.
Chapter 2 involves the preparation of regioselectively halogenated aryldioxolanes starting with the allylation of brominated and chlorinated phenols. The isomerisation of these dioxolanes into the corresponding halogenated 2-benzopyrans is then investigated.
Chapter 3 examines the regioselectivity of the Diels-Alder reaction between protected benzopyranquinones and the substituted diene 1-methoxy-1,3-bis(trimethylsilyloxy)-buta-1,3-diene 80. Such protection involves preparing the acetates and methoxymethyl ethers of the benzopyranquinones. The latter part of the chapter describes the direct bromination of benzopyranquinones.
Chapter 4 reports on the stereoselective reaction between metal phenolates and the chiral aldehyde 108 to subsequently afford naphthyldioxolanes 264, 291, 292 and 295. The rearrangement reaction of the derived naphthyldioxolane 295 is then investigated.
16
McManus, Joshua David. "A search for shorter, more convergent routes to enantiopure naphthopyrans related to the aphid insect pigments." McManus, Joshua David (2007) A search for shorter, more convergent routes to enantiopure naphthopyrans related to the aphid insect pigments. PhD thesis, Murdoch University, 2007. http://researchrepository.murdoch.edu.au/695/.
Full textAbstract:
The naphtho[2,3-c]pyran ring system is generally found amongst natural products as the 5,10- or 6,9-quinones. These compounds display a wide range of biological activities, and as such, have been synthesised by various research groups. The synthetic work described in this thesis is directed towards finding shorter, more convergent routes to enantiopure quinone A 10, quinone A' 11 and quinone-pm 13, three derivatives of the aphid insect pigments protoaphin-fb 6, protoaphin-sl 7 and protoaphin-pm 9, respectively.
The first chapter describes the previous syntheses of some naphtho[2,3-c]pyrans including those relating to the aphid insect pigment derivatives. Also detailed is the ability of these naphthopyranquinones to act as potential bioreductive alkylating and dialkylating agents. The latter part of the chapter records some of the previously achieved assemblies of quinones A 10 and A' 11 in both racemic and enantiopure form, as well as the only synthesis of enantiopure quinone-pm 13.
Chapter 2 involves the preparation of regioselectively halogenated aryldioxolanes starting with the allylation of brominated and chlorinated phenols. The isomerisation of these dioxolanes into the corresponding halogenated 2-benzopyrans is then investigated.
Chapter 3 examines the regioselectivity of the Diels-Alder reaction between protected benzopyranquinones and the substituted diene 1-methoxy-1,3-bis(trimethylsilyloxy)-buta-1,3-diene 80. Such protection involves preparing the acetates and methoxymethyl ethers of the benzopyranquinones. The latter part of the chapter describes the direct bromination of benzopyranquinones.
Chapter 4 reports on the stereoselective reaction between metal phenolates and the chiral aldehyde 108 to subsequently afford naphthyldioxolanes 264, 291, 292 and 295. The rearrangement reaction of the derived naphthyldioxolane 295 is then investigated.
17
Oosthuizen, Francois Jacobus. "Synthesis of hongconin and related naphtho[2,3-c]pyrans." Thesis, Cape Technikon, 1995. http://hdl.handle.net/20.500.11838/746.
Full textAbstract:
Thesis (MTech(Chemistry))--Cape Technikon, Cape Town,1995The naphtho[2,3-c]pyran occurs frequently in nature as derivatives of the 5,10 quinones. The most common examples include the eleutherins and protoaphins. These naturally occurring compounds have been found to possess antibiotic activity through the process of bioactivation. The possibility of appropriately substituted compounds functioning as bioreductive alkylating agents provides a logical model that has a great deal of predictive power. The thesis deals with the synthesis of some naphtho[2,3-c]pyrans to be tested biologically; the challenge being to design compounds in a biologically inactive form which become activated only subsequent to an in-vivo transformation. Chapter One describes and compares a high yielding synthesis of a naphtho[2,3c] pyran, hongconin, to a previous route.,a Racemic hongconin (29) has been synthesised from adduct (43) formed by reaction between 1-methoxycyclohexa1,4- diene (41) and 1,4-benzoquinone (42). The key steps includes Fries and Claisen rearrangements, base and cerium(lVj initiated pyran ring formation, C-4 pyran ring hydroxylation and silver(ll) mediated oxidation. The target compound (29) was tested in vitro for antimicrobial activity and compared to the results obtained for isoeleutherin (2) and its 9-demethoxy analoque (30). The spectral data, melting points and yields of the individual compounds is as described in Chapter Two.
18
Silva, Eliane de Oliveira. "Estudos sobre o metabolismo microbiano de naftoquinonas e avaliação da citotoxicidade dos metabólitos obtidos." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/60/60138/tde-26032014-094822/.
Full textAbstract:
Muitas naftoquinonas como o lapachol, podem ser encontradas em plantas da família Bignoniaceae e são conhecidas por desempenharem diversas atividades biológicas, acompanhadas, entretanto, por efeitos indesejáveis. A atividade citotóxica apresentada pelas naftoquinonas está relacionada ao aparecimento de espécies reativas de oxigênio in vivo que causam severo estresse oxidativo no interior das células. O isolapachol e a atovaquona são análogos estruturais do lapachol, sendo que a atovaquona é comercializada como fármaco para o tratamento de malária e certos tipos de pneumonia. Devido ao grande potencial biológico apresentado pelas naftoquinonas, várias tentativas no sentido de obtenção de derivados desprovidos de efeitos colaterais vêm sendo realizadas. Além disso, a determinação da segurança e eficácia dos fármacos está intimamente ligada ao estudo da formação de derivados in vivo por ocasião do metabolismo. A utilização de fungos filamentosos na predição do metabolismo que os fármacos sofreriam após administração oral, bem como de bactérias do trato gastrointestinal, pode contribuir substancialmente para a elucidação da rota metabólica de fármacos fornecendo informações sobre a geração de substâncias farmacologicamente ativas, inativas ou tóxicas e ainda sobre a produção de substâncias capazes de inibir a biotransformação de outros fármacos. Estudos de biotransformação também podem contribuir para a obtenção de novos esqueletos químicos. Dessa forma, o presente trabalho relata estudos do metabolismo microbiano do lapachol e do seu sal de potássio por bactérias do trato gastrointestinal e fungos filamentosos, além da correlação desses com as reações que ocorrem quando o isolapachol e a atovaquona são utilizados como substratos para os mesmos micro-organismos. Os experimentos de biotransformação utilizando lapachol e seu sal de potássio foram conduzidos por até dez dias, em diferentes meios de cultura, empregando-se quatro linhagens de bactérias presentes no trato gastrointestinal, além de 11 linhagens de fungos filamentosos. Foram obtidos sete metabólitos, sendo dois inéditos e dois anteriormente detectados em estudos sobre o metabolismo do lapachol em mamíferos. Durante a realização dos experimentos com o fungo filamentoso Aspergillus brasiliensis verificou-se a capacidade desse fungo em mimetizar uma reação muito importante em química orgânica, conhecida como oxidação de Hooker. As condições mais promissoras para a biotransformação do lapachol foram utilizadas nos estudos com a atovaquona e o isolapachol. A biotransformação da atovaquona possibilitou, pela primeira vez, a caracterização estrutural de um metabólito desse fármaco. Já os estudos realizados com o isolapachol permitiram inferências sobre a especificidade enzimática apresentada pelos micro-organismos avaliados. Todos os metabólitos obtidos foram submetidos aos ensaios de citotoxicidade frente a linhagens celulares normais e tumorais, o que possibilitou obter conclusões sobre a relação estrutura-atividade e sobre a citotoxicidade seletiva apresentada pelos metabólitos. Destaca-se o resultado obtido com um dos metabólitos do lapachol, ?-xiloidona, o qual se mostrou mais tóxico para a linhagem tumoral que o lapachol e não apresentou toxicidade frente à linhagem normal. O metabólito obtido a partir da biotransformação da atovaquona apresentou maior toxicidade não seletiva que a substância de partida.Several naphthoquinones, as lapachol, can be found in the Bignoniaceae family and they present several biological activities with some unwanted effects. The cytotoxic activity displayed by naphthoquinones is correlated to the presence of reactive oxygen species, which are formed in vivo and cause severe oxidative stress within cells. Isolapachol and atovaquone are structural analogs of lapachol, and atovaquone is in the market as a drug for the treatment of malaria and some types of pneumonia. Because of the great biological potential presented by naphthoquinones, several studies have been carried out to obtain derivatives without side effects. Furthermore, the drug safety and efficacy are closely related to the study of the formation of in vivo derivatives during metabolism. The filamentous fungi and the bacteria from the gastrointestinal tract can be used in the prediction of drug metabolism after oral administration, which is an interesting tool to elucidation of the metabolic pathway of drugs, providing information on the generation of pharmacologically active, inactive or toxic substances and still on the production of compounds able to inhibit the biotransformation of other drugs. Biotransformation studies can also contribute to the obtention of new chemical skeletons (hits). Thus, the present work reports the study about the microbial metabolism of lapachol and its potassium salt by filamentous fungi and bacteria from the gastrointestinal tract, beyond the correlation of the reactions that occur when the isolapachol and atovaquone are used as substrates for the same microorganisms. The biotransformations of lapachol and its potassium salt were evaluated for up to ten days, in different culture media, catalyzed by four bacteria from the gastrointestinal tract and 11 filamentous fungi strains. Seven metabolites were obtained, from which two are new and two were previously detected in the mammals metabolism of lapachol. The filamentous fungus Aspergillus brasiliensis showed to be capable of mimicking the Hooker oxidation, an important organic chemistry reaction. The best conditions for the lapachol biotransformation have been used in the studies with isolapachol and atovaquone. The atovaquone biotransformation provided, for the first time, the structural characterization of a metabolite from this drug. The studies with isolapachol allowed inferences about the enzyme specificity shown by the evaluated microorganisms. All obtained metabolites were submitted to cytotoxicity assays against human cancer and tumoral cell lines. Several conclusions about the structure activity relationship and about the selective cytotoxicity showed by the metabolites were taken. It should be highlighted the obtained result with a lapachol metabolite, ?-xyloidone, which showed to be more toxic than lapachol against tumoral cell line and did not show cytotoxicity to normal cell line. The atovaquone metabolite displayed higher toxicity than pattern structure, and this activity was not selective.
19
Chakaingesu, Chikomborero. "Synthesis and structure-activity relationship studies of 1,4-naphthoquinone derivatives as potential anti-trypanosomal agents." Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1020959.
Full textAbstract:
Human African Trypanosomiasis (HAT) is an infectious, vector-borne protozoal disease which is amongst the so-called neglected diseases. In 2000, at a summit of the United Nations, eight Millennium Development Goals (MDGs) were set, to be achieved by 2015. MDG 6 states “to combat HIV/AIDS, malaria & other diseases”. With just under 2 years to go before the end of 2015, HAT is still thriving in developing countries. The drugs currently used for the treatment of HAT are in short supply, have severe side effects and those used to treat late stages of the disease are very difficult to administer. The aforementioned challenges call for research into this neglected disease in order to develop new, safe and easy-to-use medicines. Naphthoquinones are a class of compounds shown to possess anti-parasitic activity, amongst a variety of other biological activities, and therefore this pharmacophore was selected for this study. The purpose of this study was to synthesise derivatives of 2,3-dichloro-1,4- naphthoquinone to be tested for anti-trypanosomal activity and thereafter conduct structureactivity relationship studies. A series of reactions were carried out using thiophenol, phenol and aniline nucleophiles to synthesise thioether (-S-), ether (-O-) and amino (-NH-) derivatives of 2,3-dichloro-1,4-naphthoquinone with various halogen or methyl substituents. Purification of the products was carried out by recrystallisation. Nuclear magnetic resonance (NMR), infra-red (IR) and high pressure liquid chromatography coupled to an electro-spray ionisation mass spectrometer (HPLC-ESI-MS) were the analytical methods used for structural confirmation of the products. There were eighteen 1,4-naphthoquinone derivatives that were successfully synthesised using ethanolic solutions. Unfortunately, attempts to synthesise 1,4-naphthoquinones in reactions involving 2-(trifluoro-methyl)aniline and 2-isopropyl-5-methylphenol were unsuccessful, presumably due to steric hindrance by the bulky ortho-substituents. Although the aims of the synthetic procedures were to obtain both mono- and disubstituted products by nucleophilic displacement of the chlorine atom(s) of 2,3-dichloro-1,4- naphthoquinone, only monosubstituted products were obtained from substitution with aniline and phenol nucleophiles. Thiol nucleophiles, however, selectively yielded disubstituted products only. Synthesised naphthoquinone derivatives were tested against Trypanosoma brucei and calculation of the EC₅₀ values from the obtained dose-response curves was carried out using the four parametric equation. All the 1,4-naphthoquinones showed a degree of potency, except compounds 1b, 3c and 3e, which had little or lack of potency. Structure-activity relationship studies (SARs and QSARs) were carried out to determine which structural features or functional group substituents of the naphthoquinone derivatives contribute or take away from the desired anti-trypanosomal activity. It was found that compounds with the best in vitro anti-trypanosomal potencies in the series of analogous 1,4-naphthoquinone derivatives had EC₅₀ values in the range 2.137 to 2.884 μM. The most potent compound in the series was 2-chloro-3-(4-(trifluoromethyl)phenylamino)-1,4- naphthoquinone 1e; but it was 142-fold less potent than the reference standard of melarsoprol.
20
Cardoso, Mariana Filomena do Carmo. "Síntese de derivados 5-amino-1H-pirazólicos da nor-β-lapachona com potencial perfil anticancerígeno." Niterói, 2017. https://app.uff.br/riuff/handle/1/3283.
Full textAbstract:
Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-04-04T18:00:06Z
No. of bitstreams: 1
Cardoso, Mariana Filomena do Carmo [Dissertação, 2012].pdf: 7461706 bytes, checksum: 1ba99c29719229ef773ca5d72b10c91f (MD5)Made available in DSpace on 2017-04-04T18:00:06Z (GMT). No. of bitstreams: 1 Cardoso, Mariana Filomena do Carmo [Dissertação, 2012].pdf: 7461706 bytes, checksum: 1ba99c29719229ef773ca5d72b10c91f (MD5)
Esse trabalho descreve uma nova metodologia sintética de novos derivados pirazólicos análogos a 2,2-dimetil-2,3-di-hidronafto[1,2-b]furan-4,5-diona (nor-β-lapachona), através da inserção do núcleo pirazólico a posição C-3 da nor-β-lapachona. Nesta dissertação foram sintetizados 16 (dezesseis) substâncias inéditas, sendo oito da família 3-pirazolil-2,2-dimetil-2,3-di-hidronafto[1,2-b]furan-4,5-diona contendo o núcleo pirazólico acoplado à naftoquinona os quais foram submetidos a testes biológicos para avaliação de suas atividades citotóxicas in vitro contra quatro linhagens de células tumorais humanas e uma linhagem de células normais humanas. Todas as amostras mostraram-se ativas para as linhagens tumorais e não apresentaram hemólise. A metodologia clássica para a substituição nucleofílica no carbono 3 da nor-β-lapachona desenvolvida pelo nosso grupo de pesquisa mostrou-se pouco eficaz, levando a baixos rendimentos com formação de vários produtos colaterais. Desta forma, realizou-se um estudo metodológico a fim de se viabilizar a síntese de uma família de 3-pirazolil-nor-β-lapachonas com rendimentos satisfatórios. Assim, após várias modificações nos parâmetros reacionais, observou-se que o melhor intermediário sintético era o 3-hidroxi-2,2-dimetil-2,3-di-hidronafto[1,2-b]furan-4,5-diona
This paper describes a new synthetic methodology to new pyrazole derivatives analogous to the 2,2-dimethyl-2,3-dihidronaphtho-[1,2-b]-furan-4 ,5-dione (nor-β-lapachone) by inserting the core pyrazolic on the C-3 position of the nor-β-lapachone. In this essay were synthesized 16 (sixteen) new compounds, being eight 3-pyrazolyl-2,2-dimethyl-2,3-dihidronaphtho [1,2-b]-furan-4 ,5-dione family containing core pyrazolic naphthoquinone attached to which were submitted to biological tests to evaluate their in vitro cytotoxic activities against four human tumor cell lines and normal human cell line. All samples were active for tumor cell lines and showed no hemolysis. The classical methodology for the nucleophilic substitution at carbon 3 of the nor-β-lapachone developed by our research group proved to be ineffective, leading to low yields with the formation of various side products. Thus, there was a methodological study in order to facilitate the synthesis of a family of 3-pyrazolyl-nor-β-lapachones with satisfactory yields. Then, after the various modifications on the reaction parameters, it was found that the better synthetic intermediate was the 3-hydroxy-2,2-dimethyl-2,3-dihidronaphtho-[1,2-b]-furan-4 ,5-dione
21
Shrestha, Jaya P. "Synthesis, Structure-Activity Relationship Study, and Mode of Action Study of 1,4-Naphthoquinone Based Anticancer and Antimicrobial Agents." DigitalCommons@USU, 2016. https://digitalcommons.usu.edu/etd/4925.
Full textAbstract:
Synthesizing bioactive small molecules by structural modification of 1,4-naphthoquinone was the primary goal of this research. Several bioactive compounds with anticancer, antifungal, and antibacterial activities were synthesized. All the synthetic protocols were optimized in such ways that do not require cumbersome purification.
First, a new protocol for the synthesis of NQM111 was developed. NQM111 is a highly potent anticancer agent developed in our laboratory, but the old protocol does not provide enough quantity for in vivo study. Therefore, a new safe and improved method was developed which provides enough quantity for in vivo study.
The second project involves the synthesis of 1,4-naphthoquinone conjugated with an aromatic group. These compounds are a highly potent anticancer agent with ~8-fold selectivity towards cancer cell lines than the non-cancer cell line. A mode of action study of this compound was identified, and it was observed that these compounds generate reactive oxygen species,which triggers apoptosis.
The final project involves the synthesis of 1,4-naphthoquinone based antifungal, and antibacterial compounds. These compounds are multi-cationic in nature with a hydrophobic tail. Six different analogs with varying hydrophobic tails were synthesized and tested for their antibacterial and antifungal activity. These compounds showed excellent activity against wide range of fungi including resistant strains.
22
Yamada, Hisatsugu. "Studies on naphthoquinone-sensitized one-electron photooxidation at 5-methylcytosine in DNA and its application to DNA methylation analysis." 京都大学 (Kyoto University), 2008. http://hdl.handle.net/2433/136304.
Full text
23
Santos, Evelyne Alves dos. "Estudo da Atividade CitotÃxica da Alfa-Lapachona e seu Derivado Tetrahidropirano." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10440.
Full textAbstract:
FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgicoAs quinonas sÃo metabÃlitos de ampla distribuiÃÃo na natureza que possuem diversas atividades farmacolÃgicas de importÃncia clÃnica. A naftoquinona α-lapachona demonstrou potencial como protÃtipo para o desenvolvimento de substÃncias com propriedades anticÃncer, como relatado pelo nosso grupo de pesquisa, em que o seu derivado tetrahidropirano (THP) apresentou citotoxicidade e seletividade significante contra a linhagem de melanoma MDA-MB-435. Assim, o objetivo deste trabalho foi avaliar o mecanismo de aÃÃo envolvido na citotoxicidade da α-lapachona e derivado THP em cÃlulas de melanoma MDA-MB-435. Inicialmente, avaliou-se a citotoxicidade da alfa-lapachona e derivado THP em 8 linhagens tumorais de mama e melanoma, atravÃs do ensaio do MTT, mostrando CI50 de 1,37 e 8,18 ÂM, respectivamente, apÃs 72 horas de incubaÃÃo. A seletividade do derivado THP no ensaio de Alamar Blue, demonstrou que este se apresentou 2,6 vezes menos citotÃxico para cÃlulas normais quando comparado Ãs cÃlulas tumorais. Estudos do mecanismo de morte celular na linhagem tumoral MDA-MB-435 indicaram que o derivado THP causou reduÃÃo de cÃlulas viÃveis associado com o aumento de cÃlulas nÃo-viÃveis por induÃÃo da perda de integridade da membrana plasmÃtica nas concentraÃÃes de 5 e 10 ÂM apÃs 24 horas de incubaÃÃo. A atividade citotÃxica do derivado THP nÃo està relacionada a uma fase especÃfica do ciclo celular, ativaÃÃo de caspases efetoras e formaÃÃo de espÃcies reativas de oxigÃnio, sugerindo a ocorrÃncia de um processo necrÃtico a partir de 6 horas de tratamento, demonstrado pela avaliaÃÃo da integridade de membrana. Assim, os resultados exibidos sugerem que a introduÃÃo do radical tetrahidropirano na molÃcula da α-lapachona aumenta a citotoxicidade em cÃlulas de melanoma MDA-MB-435, via necrose, o que reforÃa a importÃncia de naftoquinonas, como protÃtipo para o desenvolvimento de novos compostos sintÃticos com atividade antitumoral
Quinone metabolites are widely distributed in nature showing various pharmacological activities of clinical importance. The naphthoquinone α-lapachone has been shown to be suitable as a prototype for the development of substances with anticancer properties, as reported by our group to tetrahydropyran derivative (THP), which demonstrated significant cytotoxicity and selectivity against MDA-MB-435 melanoma line. The aim of the present work was to evaluate the mechanism of action involved in the cytotoxicity of α-lapachone and its THP derivative against MDA-MB-435 melanoma cells. Initially, we evaluated the cytotoxicity of α-lapachone and its THP derivative against 8 cell lines, by the MTT assay, showing IC50 of 1.37 and 8.18 ÂM to breast and melanoma lines, respectively, after 72 hours of incubation. The selectivity of the THP derivative in Alamar Blue assay, demonstrated that THP is 2.6 times less cytotoxic to normal cells as compared to tumor cells. Studies on the mechanism of cell death in MDA-MB-435 tumor line showed that the THP derivative caused a reduction on viable cells associated with an increase of non-viable cells by inducing loss of membrane integrity in concentrations of 5 and 10 ÂM. The cytotoxic activity of THP was independent of cell cycle, activation of effector caspases and formation of reactive oxygen species, suggesting the occurrence of a necrotic process after 6 hours of treatment, demonstrated by evaluation of membrane integrity. Thus, the data suggest that a tetrahydropyran group introduction in α-lapachone molecule enhances the cytotoxicity of MDA-MB-435 in melanoma cells, via necrosis, which reinforces the importance of naphthoquinones as prototypes for the development of new synthetic compounds with antitumor activity
24
CRUZ, Jackson Borba da. "Arcabouços de quitosana/agente antineoplásico: síntese, caracterização e aplicação." Universidade Federal de Campina Grande, 2015. http://dspace.sti.ufcg.edu.br:8080/jspui/handle/riufcg/1033.
Full textAbstract:
Submitted by Maria Medeiros (maria.dilva1@ufcg.edu.br) on 2018-06-25T14:25:31Z
No. of bitstreams: 1
JACKSON BORBA DA CRUZ - TESE (PPGCEMat) 2015.pdf: 4572910 bytes, checksum: 529c14d2c73d94769063607a9a287e65 (MD5)Made available in DSpace on 2018-06-25T14:25:31Z (GMT). No. of bitstreams: 1 JACKSON BORBA DA CRUZ - TESE (PPGCEMat) 2015.pdf: 4572910 bytes, checksum: 529c14d2c73d94769063607a9a287e65 (MD5) Previous issue date: 2015-05-22
As neoplasias constituem um conjunto de doenças que se caracterizam por uma massa anormal de tecido com crescimento descontrolado e excessivo em relação aos demais tecidos normais. De acordo com o comportamento biológico, elas podem ser classificadas em benignas ou malignas (câncer). Segundo o Instituto Nacional de Câncer (INCA), são esperados 576 mil casos novos de câncer para 2014 e 2015 no Brasil. O combate ao câncer é feito com medidas preventivas, diagnóstico precoce e tratamento. O sistema de liberação controlada de fármacos através da utilização de biomateriais poliméricos associados a compostos com ação antineoplásica pode ser empregado como alternativa de tratamento para esta patologia. Desta forma, este trabalho tem como objetivo a síntese e caracterização de arcabouços de quitosana utilizados como carreadores da droga antitumoral (1,4- Naftoquinona), cuja taxa de liberação poderá ser controlada pela utilização de um agente reticulante como o tripolifosfato de sódio (TPP), com a perspectiva da confecção de um sistema de liberação controlada de fármacos antitumorais. O método consiste na solubilização da quitosana em ácido acético, adição do fármaco, congelamento, liofilização e reticulação com TPP. Todas as amostras foram caracterizadas por Difração de Raios X (DRX), Microscopia Eletrônica de Varredura (MEV), Espectroscopia de Energia Dispersiva de Raios X (EDS), Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR) e Biodegradação Enzimática, A microscopia (MEV) evidenciou a formação de arcabouços porosos de quitosana (Q), quitosana com TPP (QT), quitosana com 1,4 – Naftoquinona (QN) e quitosana com TPP e 1,4 – Naftoquinona (QNT). Já no EDS foi observada a presença de elementos químicos como sódio, fósforo, nitrogênio, carbono e oxigênio. A reticulação dos arcabouços, comprovada pelo FTIR, DRX, Termogravimetria, Grau de Intumescimento e EDS, aumentou a taxa de degradação dos mesmos demonstrada pelo ensaio de Biodegradação Enzimática. A incorporação do fármaco foi confirmada por DRX, FTIR, Grau de Intumescimento e Termogravimetria. Desta forma, pode-se concluir que houve à formação de arcabouços reticulados e não reticulados porosos, com propriedades morfológicas e físico-químicas que podem contribuir para carrear fármacos antineoplásicos, sendo possível controlar a taxa de degradação dos mesmos e consequentemente a liberação do fármaco.
The neoplasias are a group of disorders characterized by an abnormal mass of tissue which has uncontrolled and excessive growth when compared to normal tissue. According to their biological behavior, they can be classified as benign or malignant (cancer). According to the National Cancer Institute (NCI), it is expected that there will be 576,000 new cancer cases in Brazil during 2014 and 2015. The fight against cancer is done with preventive measures, early diagnosis and treatment. The controlled release system of drugs through the use of polymeric biomaterials associated with the compounds that have an antineoplastic action can be used as an alternative treatment for this disease. Thus, this work has as the objective, the synthesis and characterization of chitosan scaffolds used as carriers for antitumor drugs (1,4 Naftoquinona), whose release rate can be controlled by using a crosslinking agent such as sodium tripolyphosphate (TPP), with the prospect of making a controlled release system for antitumor drugs. The method comprises in the solubility of chitosan in acetic acid, drug addition, freezing the material, lyophilization and crosslinking with TPP. All samples were characterized by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and Enzymatic Biodegradation. The Microscopy (SEM) showed the formation of porous scaffolds of chitosan (Q), chitosan with TPP (CT), chitosan with 1.4 - Naftoquinona (QN) and chitosan with TPP and 1.4 - Naftoquinona (QNT). EDS showed the presence of chemical elements such as sodium, phosphorus, nitrogen, carbon and oxygen. The crosslinking of the scaffolds, proven by FTIR, XRD, Thermogravimetry, Degree of Swelling and EDS, increased its rate of degradation thereof, as demonstrated by the Enzymatic Biodegradation test. The incorporation of the drug was confirmed by XRD, FTIR, Degree of Swelling and Thermogravimetry. Thus, it can be concluded that there was the formation of crosslinked and non-crosslinked porous scaffolds, with morphological and physicochemical properties that can contribute to the carrying of antineoplastic drugs, being possible to control their degradation rate and consequently drug release.
25
Liu, Yixi. "Isolation and Structure Elucidation of Anticancer and Antimalarial Natural Products." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/52259.
Full textAbstract:
As part of an International Cooperative Biodiversity Group (ICBG) program and a continuing search for antiproliferative natural products from the Madagascar rainforest, and a collaborative research project established between Virginia Tech and the Institute for Hepatitis and Virus Research (IHVR) focusing on searching for bioactive natural products from tropical forests in South Africa, 20 extracts were selected for investigation based on their antiproliferative activities against A2780 human ovarian cancer cell line or antimalarial activities against the Dd2 strain of Plasmodium falciparum. Bioassay-guided fractionation of seven of the extracts yielded twenty new compounds and twenty-four known compounds, and their structures were elucidated by using a combination of 1D (1H and 13C) and 2D NMR spectroscopy including COSY, HASQC, HMQC, HMBC, and NOESY sequences, mass spectrometry, UV, IR, ECD, optical rotation, and chemical conversions. In addition, ten known compounds were isolated from another five of the extracts, while studies on the remaining extracts were suspended due to loss of activity, unworkable small amounts of material, or low structural interest.
The plants and their metabolites are discussed in the following order: five new antimalarial 5,6-dihydro-𝛼-pyrones and six bicyclic tetrahydro-𝛼-pyrone derivatives from Cryptocarya rigidifolia (Lauraceae); two new and five known antiproliferative lignans from Cleistanthus boivinianus (Phyllanthaceae); two new and two known antiproliferative sesquiterpenes lactones from Piptocoma antillana (Asteraceae); one new antiproliferative 1,4-naphthoquinone, one known antiproliferative isoflovonoid, and five known antiproliferative stilbenoids from Stuhlmannia moavi (Leguminosae); four known antiproliferative bisbenzylisoquinoline alkaloids from Anisocycla grandidieri (Menispermaceae); one new and two known antiproliferative butanolides, and two new antiproliferative secobutanolides from Ocotea macrocarpa (Lauraceae); one new antiproliferative and five known antiproliferative diterpenoids from Malleastrum rakotozafyi (Meliceae); and 10 known compounds from Monoporus sp. (Myrsinaceae), Premna corymbosa (Verbenaceae), Premna perplexanes (Verbenaceae), Epallage longipes (Asteraceae), and Cinnamosma fragrans (Canellaceae).Ph. D.
26
Bulovas, Arūnas. "Self-assembled monolayers of biomimetic (methyl)naphthoquinone omega-mercapto derivatives on gold and silver surfaces: electrochemical and spectroscopic studies of redox conversion and structure." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20100204_103028-93997.
Full textAbstract:
A large set of biomimetic 1,4-naphthoquinone mercapto derivatives varying in the side-chain length and intrachain functional groups was synthesized. Interfacial redox processes and fine structure of self-assembled monolayers formed from newly synthesized compounds on gold and silver were studied by cyclic voltammetry and surface-enhanced Raman spectroscopy.Mixed monolayers of naphthoquinone derivatives and different redox inactive alkylthiols were studied. Low-density naphthoquinone-based monolayers were studied more thoroughly.Sintezuotas didelis rinkinys biomimetinių 1,4-naftochinono merkapto darinių, besiskiriančių šoninės grandinės ilgiu ir įterptomis funkciškai aktyviomis grupėmis. Jų monosluoksnių ant aukso ir sidabro paviršių struktūra ir redokso virsmai ištirti ciklinės voltamperometrijos ir paviršiaus sustiprintos Ramano spektroskopijos metodais. Ištirta monosluoksnio paviršinės koncentracijos ir kitų parametrų priklausomybė nuo modifikacinio tirpalo koncentracijos. Palyginti mišrūs naftochinono darinių ir skirtingų alkantiolių, neturinčių redokso aktyvumo, monosluoksniai.
27
Zhang, Jianjun. "Library Synthesis of Anticancer and Antibacterial Agents via Azide Chemistry." DigitalCommons@USU, 2010. https://digitalcommons.usu.edu/etd/711.
Full textAbstract:
Various anticancer and antibacterial agents have been synthesized via azide chemistry by taking advantage of carbohydrate. Starting from the synthesis of 14 glycosyl azides, a library of carbohydrate-oxazolidinone conjugates and a library of carbohydrate-cyclopamine conjugates with biological interests were synthesized based on a highly efficient "click reaction" assisted by sonication. Some of the conjugates have improved solubility and enhanced anticancer activity. A library of neomycin B derivatives with various modifications at the 5" position has been synthesized. Two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Antibacterial activities were measured when combined with other clinically used antibiotics and significant synergistic activities were observed. Three different classes of aryl N-glycosides have been synthesized by employing 1,4-naphthoquinone and glycosyl azides undergoing a [2+3] cycloaddition. Alkyl azides can also undergo the same cycloaddition. After the removal of the protecting group, a library of 9,10-anthraquinone derivatives with potential anticancer activity and a library of 2-aminomethylene-1,3-indanediones with novel antibacterial activity have been developed, respectively. A one-pot three-component [2+3] cycloaddition for the synthesis of 1-alkyl 1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione and 2-alkyl 2H-naphtho[2,3-d][1,2,3] triazole-4,9-dione has been developed. By taking the advantage of their difference in basicity, both products can be obtained in good purity. Using an allylic azide rearrangement, a convenient method has been developed for the synthesis of several 2',3'-dideoxyaminoglycosides. The antibacterial activity of these novel aminoglycosides also confirms the indispensable role of the 2'-NH2 group for both neomycin and kanamycin classes of aminoglycosides. A novel structural motif containing the hexylaminocarbonyl groups at O-5 and/or O-6 of 2',3'-dideoxyneamine could lead to the production of new aminoglycosides against resistant bacteria.
28
Lin, Zhu Qing. "Protective effects of, 2-methoxy-6-acetyl-7-methyljuglone, a naphthoquinone in Polygonum cuspidatum (Hu-Zhang), against PC12 apoptosis induced by tert-butyl hydroperoxide." Thesis, University of Macau, 2009. http://umaclib3.umac.mo/record=b2158130.
Full text
29
Jelly, Renee Michelle. "Natural products as novel reagents for the detection of latent fingermarks." Thesis, Curtin University, 2010. http://hdl.handle.net/20.500.11937/2079.
Full textAbstract:
The ability to detect latent fingermarks on porous surfaces, such as paper-based documents, is extremely important in resolving criminal cases. Detection methods that target amino acids present in latent fingermark deposits have achieved widespread use. This is due to the chemical stability of this component of the eccrine secretion and the binding of the amino acids to paper fibres, thus resulting in a good representation of the fingermark. This dissertation presents studies into the ability of naphthoquinones to develop latent fingermarks on paper surfaces. These compounds represent a completely new class of fingermark detection reagents.Lawsone (2-hydroxy-1,4-naphthoquinone), the compound thought to be responsible for the staining properties of henna, was found to react with latent fingermarks on porous surfaces to yield purple/brown images that exhibit photoluminescence without further treatment. Luminescence spectrophotometry of developed amino acid spots on paper indicated that lawsone is reacting with the amino acids in latent fingermarks. A mechanism for this reaction is postulated.Lawsone is a naphthoquinone, a group of compounds, which are known for reacting with amino acids to produce highly coloured compounds. On this basis, the following naphthoquinones were selected for subsequent investigations: 1,4-dihydroxy-2-naphthoic acid; 1,2-naphthoquinone-4-sulfonate; 2-methoxy-1,4-naphthoquinone; and 2-methyl-1,4-naphthoquinone. All of the tested compounds yielded brown visible impressions, which also exhibited luminescence. Luminescence spectrophotometry revealed differences in photoluminescence characteristics for fingermarks developed with the different naphthoquinones with excitation over the range 530-590 nm. Luminescence spectrophotometry of developed amino acid spots on paper confirmed that the naphthoquinones were reacting with amino acids in the latent fingermarks.Fingermarks and amino acids on cellulose thin layer chromatography plates were developed with lawsone and the additional selected naphthoquinones listed above. These specimens were then subjected to analysis by synchrotron infrared microscopy. Despite significant issues with the presence of a cellulose background signal, it was possible to successfully obtain spectra of the reaction products in-situ. In an attempt to rationalise these results, lawsone was reacted with glycine in solution to afford a mixture of two coloured compounds. These compounds were characterised and one was tentatively identified as 2-amino-1,4-naphthoquinone or a structural isomer thereof. A structure could not be assigned to the second compound, however nuclear magnetic resonance spectroscopy indicated a symmetrical dimer, containing two lawsone moieties.Some preliminary results are presented for a screening of additional natural product based colour forming compounds as latent fingermark detection reagents. Two compounds, juglone and alizarin, were found to successfully develop latent fingermarks on paper. In addition a systematic retrosynthetic approach was taken to explore the potential of a natural dye precursor as a fingermark reagent. Finally, a serendipitous discovery of the skin dyeing properties of 6-N,N-dimethylaminofulvene, provided an additional route to a possible class of fingermark detection compounds unrelated to ninhydrin. These preliminary studies indicate potential strategies for further research towards novel latent fingermark reagents for porous surfaces.
30
Ta, Chieu Anh Kim. "Bacterial Biofilm Inhibition and Antifungal Activity of Neotropical Plants." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32419.
Full textAbstract:
This thesis examined the antimicrobial activity of select neotropical plants from Costa Rica and traditional Q’eqchi Maya medicines from Belize. In particular the potential for interference with bacterial quorum sensing (QS) and biofilm formation as well as fungal growth were assessed. Of one hundred and twenty six extracts collected from Costa Rica, one third showed significant QS inhibition while 13 species displayed more biofilm inhibitory activities than the positive control allicin. The active species belonged to the Lepidobotryaceae, Melastomataceae, Meliaceae, Sapindaceae, and Simaroubaceae. Twelve Marcgraviaceae species were tested for the same biological activities; of these, three showed similar QS inhibition to that of the positive control Delisea pulchra (Greville) Montagne and five with at least 30% biofilm inhibition. Only one species inhibited fungal growth – Marcgravia nervosa Triana & Planch. Bioassay-guided isolation of this plant resulted in the identification of the active principle as a naphthoquinone, with a minimum inhibitory concentration (MIC) ranging from 85 to 100 μM against Saccharomyces cerevisiae. Similarly, sixty one Q’eqchi’ Maya medicinal plant species were evaluated for their antimicrobial activities. Of these, four species showed more QS inhibition than D. pulchra, seven with comparable biofilm inhibitory activities that of allicin, and two with similarly antifungal activity to berberine. Two spirostanol saponins were isolated from Cestrum schlechtendahlii G.Don, an active antifungal plant. The major saponin showed growth inhibition against Saccharomyces cerevisiae and Fusarium graminearum, with MICs of 16.5 μM and 132 μM, respectively. Further analyses of this compound using chemical genomics suggested that its antifungal mechanism of action is pleiotropic, affecting multiple targets. Taken together, these findings showed that neotropical plants and traditional Q’eqchi’ Maya medicines contain phytochemicals that interfere with bacterial biofilm formation and quorum sensing as well as fungal growth.
31
Moyo, Buhle. "The screening and characterisation of compounds for modulators of heat shock protein (Hsp90) in a breast cancer cell model." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1004129.
Full textAbstract:
Breast cancer is a leading cause of cancer death in Africa. Hsp90 has been identified as a target for anti-cancer treatments as its inhibition results in the disruption and ubiquitin–proteasome degradation of activated oncoproteins. Currently, there are no US Food and Drug Administration approved Hsp90 inhibitor drugs and existing Hsp90 inhibitors such as geldanamycin and novobiocin are hepatotoxic and display a low affinity for Hsp90, respectively. Therefore, there is a need for the development of Hsp90 inhibitors with improved inhibitory properties. In this study twelve natural compounds bearing a quinone nucleus were screened and characterised for the modulation of Hsp90. The compounds analysed formed three series; the sargaquinoic acid (SQA), naphthoquinone, and pyrroloiminoquinone alkaloid series. Certain compounds exhibited half maximal inhibitory concentrations of between 3.32 μM and 12.4 μM, while others showed no antiproliferative activity at concentrations of up to 500 μM in the MDA-MB-231 breast adenocarcinoma cell line. Immunofluorescence and Western analyses indicated that the modulation of Hsp90 and partner proteins by SQA was more similar to that of novobiocin. Isothermal titration calorimetry analyses suggested that SQA interacted with Hsp90β with a low affinity, and saturation-transfer difference nuclear magnetic resonance confirmed that this interaction with Hsp90β occurred through the methyl moiety bound to 1, 4 benzoquinone of SQA. Pulldown assays indicated SQA disrupted the association between Hsp90 and Hop dose-dependently, more similarly to novobiocin. Immunofluorescence and Western analyses performed on naphthoquinone and pyrroloiminoquinone alkaloid compounds indicated modulation of Hsp90 and Hsp90 partner proteins by the compounds. Naphthoquinone compounds were prioritised for analysis for binding to Hsp90β over the pyrroloiminoquinone alkaloid compounds. Lapachol interacted with Hsp90β with a low affinity however; this interaction was thought to be too weak to disrupt the association of Hsp90 and Hop. The remaining naphthoquinone compounds showed no interaction with Hsp90β, thus allowing the determination of a preliminary structure-activity relationship for these compounds. To the best of our knowledge, this is the first study to describe a systematic subcellular analysis of the effects of geldanamycin and novobiocin in comparison to sargaquinoic acid and compounds of the naphthoquinone and pyrroloquinoline scaffold on Hsp90 and its partner proteins.Microsoft� Word 2010
Adobe Acrobat 9.54 Paper Capture Plug-in
32
Castro, Murilo Fagundes de. "Avaliação da atividade anti-trypanosoma cruzi in vitro e in vivo de derivados de vitamina K." Centro de Pesquisas Gonçalo Moniz, 2012. https://www.arca.fiocruz.br/handle/icict/7182.
Full textAbstract:
Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-10-18T18:15:09Z
No. of bitstreams: 1
Murilo F. Castro. Avaliação da atividade,,, 2012.pdf: 1468986 bytes, checksum: 7b9241cb49aba27e80628022c24eb12a (MD5)Made available in DSpace on 2013-10-18T18:15:09Z (GMT). No. of bitstreams: 1 Murilo F. Castro. Avaliação da atividade,,, 2012.pdf: 1468986 bytes, checksum: 7b9241cb49aba27e80628022c24eb12a (MD5) Previous issue date: 2012
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
A doença de Chagas (DC) é considerada um agravo ainda negligenciado. Atualmente, estima-se cerca de 10 milhões de pessoas infectadas pelo Trypanosoma cruzi, em todo o mundo, principalmente na América Latina. Sabe-se que alguns derivados de naftoquinonas podem agir sobre a tripanotiona redutase (TR), enzima específica dos tripanossomatídeos responsável pelo controle oxidativo celular. A inibição da TR favorece um processo oxidativo e morte do protozoário. Este trabalho teve como objetivo investigar o potencial anti-T.cruzi da fitomenadiona, (K1) e menadiona (K3), ambas vitaminas K derivadas de naftoquinonas. Com este propósito, o efeito tripanocida de K1 e K3 foi avaliado através de ensaios in vitro com as formas tripomastigotas e epimastigotas do T. cruzi nas cepas Colombiana e Y utilizando os testes de inibição, citotoxicidade dos compostos, ensaio de infecção em macrófagos, avaliação de alterações ultraestruturais, bem como ensaio em in vivo para avaliação na redução da parasitemia. Os valores de IC50 mais significativos para formas tripomastigotas do T. cruzi foram 27,55 μM para K1, 2,19 μM para K3 e 12,46 μM para o benzonidazol, a droga padrão. Contudo, o tratamento com a vitamina K1 não reduziu a parasitemia in vivo, que permaneceu alta assim como a do controle tratado com veículo. A vitamina K3 foi capaz de inibir ambas as cepas e diferentes formas do parasito em ensaios in vitro. No ensaio de infecção de macrófagos, a vitamina K3 em concentração de 21,4 μM inibiu de forma mais significativa a infecção de células em relação à droga padrão, em concentração de 38,4 μM. Apesar da citotoxicidade mais elevada, esta droga apresentou uma seletividade maior ao parasito do que a células de mamíferos e, em baixas doses, causou a redução na parasitemia in vivo. As avaliações ultraestruturais por microscopia eletrônica de transmissão evidenciaram alterações celulares induzidas por estes compostos, destacando-se a tumefação do cinetoplasto e a presença de vacúolos. A quantificação ultraestrutural na avaliação por microscopia eletrônica de varredura demonstrou alterações em cerca de 80% dos parasitos observados quando tratados com K3 a 5 μM. Nossos resultados demonstram o efeito anti-T. cruzi das moléculas testadas e sugerem que estas possam servir de base para o desenho de novos compostos candidatos a fármacos para o tratamento da doença de Chagas.
Chagas disease (AD) is considered a neglected disease. Currently, it is estimated 10 million people infected with Trypanosoma cruzi, worldwide, mostly in Latin America. It is known that some derivatives of naphthoquinones can act on the trypanothione reductase (TR), specific enzyme of trypanosomatids responsible for controlling oxidative stress. Inhibition of TR favors an oxidative process and death of the parasite. This work aimed to investigate the potential anti-T. cruzi of phytomenadione, (K1) and menadione (K3), both vitamin K derived from naphthoquinones. For this purpose, the trypanocidal effect of K1 and K3 was evaluated by in vitro assays with epimastigotes and trypomastigotes of T. cruzi in strains Colombian and Y using the inhibition tests, cytotoxicity of compounds of infection in macrophages test, evaluation of ultrastructural alterations as well as in vivo test to evaluate the reduction of the parasitemia. The best IC50 values to trypomastigote forms of T. cruzi were 27.55 μM to K1 and 2.19 μM to K3, compared to 12.46 μM of benznidazole, the standard drug. However, the treatment with vitamin K1 did not reduce parasitemia in vivo, which remains high similar to the vehicletreated control group. Vitamin K3 was able to inhibit both strains and different forms of the parasite in in vitro assays. In macrophage infection assay, vitamin K3 at a concentration of 21.4 μM significantly inhibited T. cruzi infection of cells when compared to the standard drug (benznidazole) in a concentration of 38.4 μM. Although this compound had a high cytotoxicity, vitamin K3 showed greater selectivity than the parasite mammalian cells, and in a low dose caused a reduction in parasitemia in vivo. The ultrastructural evaluation by transmission electron microscopy revealed cellular alterations induced by these compounds, especially the swelling of the kinetoplast and the presence of vacuoles. The ultrastructural quantification in the evaluation by scanning electron microscopy showed changes in about 80% of parasites observed when treated with 5 μM K3. Our results demonstrate the anti-T. cruzi molecules tested, suggesting that they may serve as a basis for designing new drug candidate compounds for the treatment of Chagas disease.
33
NASCIMENTO, Wilson Silva do. "Síntese de 1,2,3- triazóis ligados a 1,4- naftoquinona via reação de cicloadição 1,3- dipolar." Universidade Federal Rural de Pernambuco, 2011. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/6380.
Full textAbstract:
Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T15:40:19Z
No. of bitstreams: 1
Wilson Silva do Nascimento.pdf: 1102619 bytes, checksum: f3fd4580e9425c165601806a91092eda (MD5)Made available in DSpace on 2017-02-15T15:40:19Z (GMT). No. of bitstreams: 1 Wilson Silva do Nascimento.pdf: 1102619 bytes, checksum: f3fd4580e9425c165601806a91092eda (MD5) Previous issue date: 2011-02-15
In the present study was performed the synthesis of a new series of 1,2,3- triazole derivative 1,4-disubstituted naphthoquinone group containing the position of a heterocyclic ring from the reaction of 1,3-dipolar cycloaddition between the two precursor azido-1,4-naphthoquinone and 10 terminal alkynes, using a method that employs the use of CuI as the catalytic species for the regioselective formation of the triazole and acetonitrile as solvent. Other methods were also tested, including the one described by using Sharpless reducing environment, however, these methods were less effective or not promoted the formation of the triazole ring. Two of these triazoles had obtained the hydroxyl groups present in its structure acetylated methodology developed in our laboratory using acetic anhydride and montmorillonite K-10 by ultrasound, a total number of 12 new structures of [1,2,3]-triazole 1,4- disubstituted. A second route to obtain 1,4-disubstituted triazoles connected to 1,4- naphthoquinone was proposed from the reaction between 2-ethynyl-1,4- naphthoquinone and azido compound, for it was synthesized the 2-(3-hydroxy-3- metilbutinil)-1,4-naphthoquinone. However, the subsequent reaction of deprotection of this compound, as well as the synthesis of the precursor 2-trimethylsilyl-1,4- naphthoquinone did not work. All the products of unknown structures were characterized by 1H NMR and 13C NMR, elemental analysis, LC-MS and infrared.
No presente trabalho foi realizada a síntese de uma nova série de derivados 1,2,3-triazólicos 1,4-dissubstituídos contendo o grupo naftoquinona na posição 1 deste anel heterocíclico a partir da reação de cicloadição 1,3-dipolar entre o precursor 2-azido-1,4-naftoquinona e 10 alcinos terminais, utilizando um método que emprega o uso de CuI como espécie catalítica para a formação regiosseletiva do anel triazólico e acetonitrila como solvente. Outros métodos também foram testados, entre eles o descrito por Sharpless que utiliza meio redutor, no entanto, estes métodos mostraram-se menos eficiente ou não promoveram a formação do anel triazólico. Dois destes triazóis obtidos tiveram os grupos hidroxilas presente em sua estrutura acetilados por metodologia desenvolvida em nosso laboratório utilizando anidrido acético e montmorillonite K-10 em ultra som, totalizando uma série de 12 novas estruturas de [1,2,3]-triazóis 1,4-dissubstituídos. Uma segunda rota para a obtenção dos derivados triazólicos 1,4-dissubstituídos ligados à 1,4- naftoquinona foi proposta a partir da reação entre o 2-etinil-1,4-naftoquinona e azido composto, para isso, foi sintetizado o 2-(3-hidroxi-3metilbutinil)-1,4-naftoquinona. No entanto, a subseqüente reação de desproteção deste composto, assim como, a síntese do precursor 2-trimetilsilil-1,4-naftoquinona não funcionou. Todos os produtos obtidos de estruturas inéditas foram caracterizados por espectroscopia de RMN 1H e RMN 13C, análise elementar, LC-MS e infravermelho.
34
Gabriel, Gabriela Hadler. "Propriedades citotóxicas da Beta-Lapachona em células de osteossarcoma in vitro." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/7150.
Full textAbstract:
Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-04-13T17:22:48Z
No. of bitstreams: 2
Dissertação - Gabriela Hadler Gabriel - 2017.pdf: 1069284 bytes, checksum: 7c190e383bf6069f54d2eff26158427f (MD5)
license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-04-17T11:13:33Z (GMT) No. of bitstreams: 2 Dissertação - Gabriela Hadler Gabriel - 2017.pdf: 1069284 bytes, checksum: 7c190e383bf6069f54d2eff26158427f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)
Made available in DSpace on 2017-04-17T11:13:33Z (GMT). No. of bitstreams: 2 Dissertação - Gabriela Hadler Gabriel - 2017.pdf: 1069284 bytes, checksum: 7c190e383bf6069f54d2eff26158427f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-09
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Osteosarcoma is the main primary bone tumor, with unfavorable prognosis, high mortality and high incidence of metastases. The treatment of choice is the removal of the tumor associated with combined chemotherapy, whose adverse effects allude to the increasing need to develop new drugs. The plants constitute a large natural reserve of compounds that have medicinal and therapeutic properties, such as lapachol and its derivative, β-lapachone. The aim of this study was to evaluate the cytotoxic effects of β-lapachone in osteosarcoma cells cultured in vitro. Cells were cultured and treated with β-lapachone at different concentrations and times of exposure. Tripan blue exclusion, tetrazolium reduction and cell survival assay methods were performed to evaluate the effects of the compound on the cells. Cells treated with 0,1μM β-lapachone showed lower initial cytotoxicity in the 24h time, whereas those submitted to 1,0μM showed less viability after 72h of treatment. Cytotoxicity increased as the concentration and time of exposure increased. The lowest IC50 (0,148μM) was observed in treated cells for 72h. Cell growth after treatment was lower in the 1.0μl group after 72h and the highest cell growth was observed under a concentration of 0.1μl after 24h. There was no difference between groups for cell proliferation after treatment, and the cell survival fraction was lower after 72h of exposure. It was concluded that β-lapachone has cytotoxic effects on osteosarcoma cells cultured in vitro.
O osteossarcoma é o principal tumor ósseo primário, com prognóstico desfavorável, alta mortalidade e elevada incidência de metástases. O tratamento de escolha é remoção do tumor associada à quimioterapia combinada, cujos efeitos adversos aludem à necessidade crescente de desenvolver novos medicamentos. As plantas constituem grandes reservas naturais de compostos que possuem propriedades medicinais e terapêuticas, como o lapachol e seu derivado, a β lapachona. O objetivo desse estudo foi avaliar os efeitos citotóxicos da β lapachona em células de osteossarcoma cultivadas in vitro. As células foram cultivadas e tratadas com a β lapachona em diferentes concentrações e tempos de exposição. Foram realizados os métodos de exclusão com azul de Tripan, redução do tetrazólio e ensaio de sobrevivência celular para avaliar os efeitos do composto sobre as células. As células tratadas com 0,1μM de β lapachona apresentaram menor citotoxicidade inicial, no tempo de 24h, enquanto aquelas submetidas a 1,0μM apresentaram menor viabilidade após 72h de tratamento. A citotoxicidade aumentou de acordo com o aumento da concentração e tempo de exposição. O menor IC50 (0,148μM) foi observado nas células tratadas por 72h. O crescimento celular após o tratamento foi menor grupo sob concentração de 1,0µl após 72h e o maior crescimento celular foi observado sob concentração de 0,1µl após 24h. Não houve diferença entre grupos quanto à proliferação celular após o tratamento tendo a fração de sobrevivência das células sido menor após 72h de exposição. Concluiu-se que β lapachona apresenta efeitos citotóxicos em células de osteossarcoma cultivadas in vitro.
35
SILVA, Mauro Gomes da. "Síntese de derivados 2,3-diino-1,4-naftoquinonas usando a reação de Sonogashira e avaliação da atividade citotóxica." Universidade Federal Rural de Pernambuco, 2012. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/6364.
Full textAbstract:
Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T13:39:52Z
No. of bitstreams: 1
Mauro Gomes da Silva.pdf: 2235103 bytes, checksum: 2f7922e62d0e9e6cd2bbc309f61aa8f1 (MD5)Made available in DSpace on 2017-02-15T13:39:52Z (GMT). No. of bitstreams: 1 Mauro Gomes da Silva.pdf: 2235103 bytes, checksum: 2f7922e62d0e9e6cd2bbc309f61aa8f1 (MD5) Previous issue date: 2012-03-14
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
In the present study ten 2,3-diyne-1,4-naphthoquinone derivatives were synthesized by Sonogashira coupling reaction between the 2,3-dibromo-1,4- naphthoquinone and several functionalized terminal alkynes using a catalytic complex of palladium (II) and CuI. Alkynes are among phenylacetylene, 1-ethyl-4- methoxybenzene, 2-methyl-3-butyn-2-ol, 1-ethynyl-1-cyclohexanol, 4-pentyn-2-ol, 4- pentyn-1-ol, 1-pentyne, 1-hexyne, 1-octyne and 1-decyne. The yields of products obtained ranged 15 to 55%. The enediynes having hydroxyl groups, in their structures such as 2,3-di(3-hydroxy-3-methylbut-1-yn-1-yl)-, 2,3-di[(1- hydroxycyclohexyl)ethynyl]- and 2,3-di(5-hydroxypent-1-yl)-1,4-naphthoquinone were subjected to acetylation reaction using acetic anhydride and montmorillonite clay K- 10 under sonication, thereby obtaining three new enediyne derivatives with yields ranging from 56 to 71%. The compounds were all characterized by 1H NMR and 13C NMR spectra, IR and MS-LC. These compounds containing the 1,4-naphthoquinone nucleus and acetylenic substituents in the quinonoid ring form a enediyne system (Z-3-ene-1,5-diyne) highly reactive, possibly subject to Bergman cycloaromatization, with potential antitumor activity. The enediynes underwent evaluation of the cytotoxic potential against three tumor cell lines, OVCAR-8 (ovarian adenocarcinoma - human), PC-3M (metastatic prostate cancer - human), NCI-H358M (bronchoalveolar lung carcinoma - human), presenting, in general, satisfactory results for inhibition of cell growth. The compound 2,3-di(3-hydroxy-3-methylbut-1-yn-yl)-1,4-naphthoquinone where said among the substances analyzed by presenting a lower IC50 (˂ 2 μg/mL) for three cell lines tested, which is characterized as a potent cytotoxic agent.
No presente trabalho foram obtidos dez derivados 2,3-diino-1,4- naftoquinonas, entre estes sete são inéditos na literatura, empregando a reação de acoplamento de Sonogashira entre o 2,3-dibromo-1,4-naftoquinona e diversos alquinos terminais funcionalizados, utilizando um complexo catalítico de paládio (II) e CuI. Entre os alquinos estão o fenilacetileno, o 4-metoxifenilacetileno, o 2-metil-3- butin-2-ol, o 1-etinil-1-cicloexanol, o 4-pentin-2-ol, o 4-pentin-1-ol, o 1-pentino, o 1- hexino, o 1-octino e o 1-decino. Os rendimentos dos produtos obtidos variaram entre 15-55%. Os enediinos que possuem grupos hidroxilas presentes em suas estruturas, como o 2,3-di(3-hidroxi-3-metilbut-1-in-il)-, o 2,3-di[(1-hidroxicicloexil)etinil]- e o 2,3- di(5-hidroxipent-1-il)-1,4-naftoquinona, foram submetidos à reação de acetilação utilizando anidrido acético e argila montmorillonita K-10 em ultrassom, obtendo assim, três novos derivados enediinos com rendimentos que variaram de 56-71%. Os compostos obtidos foram todos caracterizados por espectros de RMN 1H e RMN 13C, LC-MS e IV. Estes compostos contendo o núcleo 1,4-naftoquinona e substituintes acetilênicos no anel quinônico formam um sistema enediino (Z-3-eno-1,5-diino) altamente reativo, possivelmente sujeito a cicloaromatização de Bergman, com potencial atividade antitumoral. Os enediinos foram submetidos à avaliação do potencial citotóxico em três linhagens de células tumorais, OVCAR-8 (adenocarcinoma de ovário – humano), PC-3M (carcinoma de próstata metastático – humano), NCI-H358M (carcinoma bronquioalveolar de pulmão – humano, apresentando, no geral, resultados satisfatórios para inibição do crescimento celular. O composto 2,3-di(3-hidroxi-3-metilbut-1-in-1-il)-1,4-naftoquinona se destacou dentre as substâncias analisadas por apresentar menor CI50 (˂ 2 μg/mL) para as três linhagens de células testadas, o que o caracteriza como potente agente citotóxico.
36
Araújo, Morgana Vital de. "Investigação leishmanicida de protótipos de origem natural e sintéticos." Universidade Federal de Alagoas, 2016. http://www.repositorio.ufal.br/handle/riufal/1467.
Full textAbstract:
Leishmaniasis is among the most neglected diseases in the world. Currently, the drugs available for its treatment are limited and highly toxic, so the search for more effective and safer medicines is necessary. Thus, this paper aims to investigate the leishmanicidal activity of new natural, and synthetic. Two series of new 1,4-naphthoquinone derivatives were synthesized. The series of bis-2-hydroxy-1,4-naphthoquinone substituents exhibited significant activity against Leishmania amazonensis and Leishmania braziliensis promastigotes, six compounds showed good activity without toxic effects against the host cell. Moreover, compound 3a, which was selected to an in vivo infection assay with Leishmania amazonensis, reduced the size of the infected ear, but did not reduce parasite burden of the ear and draining lymph node. Furthermore, treatment with 3a induced no change in spleen weight or changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and urea levels. The series of 2-N,N'-dialkylamino-1,4-naphthoquinone substituents showed activity against promastigotes of L. chagasi and L. amazonensis, especially 1d, 1h and 1i, which exhibited L. amazonensis promastigote growth inhibition over 50%, and 1d, 1e, 1f, 1h, 1k and 1n derivatives which inhibited the growth of L.chagasi promastigotes over 70%. In the assay against the amastigote intracellular forms, 1a, 1b, 1c, 1d, 1h, 1i, 1k and 1m derivatives presented significant activity. The flavonoids SP1, SP2, and SP3 and S. palodosum crude extract inhibited the growth of promastigotes and amastigotes of L. amazonensis and L. chagasi. Moreover, SP4 inhibited the growth of promastigotes L. amazonensis. In regard an intracellular forms growth inhibition, SP1, SP3, and crude extract were active significantly. Furthermore, in the in vivo assay of infection with L. amazonensis, the compounds SP1 and SP3 reduced the parasitic burden on the infected ear, but did not reduce parasite burden on draining lymph node. On Leishmania cell cycle analysis, it was observed that SP1 and SP3 induced modifications on S and G2/M phases of cell cycle. In addition, SP3 induced death by apoptosis, and changed autophagy intensity, suggesting anti-proliferative activity at the concentration of 100 μM. The compound 3,7,3',4'-tetra-O-methylquercetin (retusin) inhibited the growth of promastigotes and amastigotes of L. amazonensis and L. chagasi. In the infection assay using hamsters infected with L. chagasi, retusin decreased the parasite burden in the spleen of infected animals. However, in the in vivo assay of infection using Balb/c mice infected with L. amazonensis, retusin did not reduce the parasitic load in the ear and draining lymph node. Moreover, retusin induced morphological alterations in L. chagasi promastigotes observed by scanning electron microscopy. In addition, retusin induced death by apoptosis at the concentration of 100 μM, which is probably not dependent on caspases; besides retusin inhibited Leishmania topoisomerases. The results indicate that the 1,4-naphthoquinone derivatives and flavonoid compounds derived from S. paladosum are active against Leishmania, mainly 1a, 1b, 1c, and 1m, which were active against Leishmania in the in vitro assays, without induce damage in host cells; and SP1, SP3, and rutesin, which were active in vivo by intraperitoneal route, suggesting they can be useful lead compounds candidates for antileishmanial drugs.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A leishmaniose está entre as doenças mais negligenciadas do mundo. Atualmente, os medicamentos disponíveis para o tratamento são limitados, de toxicidade elevada e cepas de Leishmania spp. têm apresentado resistência aos tratamentos preconizados. Assim faz-se necessário a busca de medicamentos mais eficazes e mais seguros. Dessa forma, este trabalho visa investigar a atividade leishmanicida de novos compostos de origem natural e sintéticos. Foram sintetizados duas séries de novos derivados 1,4-naftoquinonas. A série com substituintes bis-2-hidroxi-1,4-naftoquinona exibiram atividade significante contra promastigotas de Leishmania amazonensis e Leishmania braziliensis, seis destes compostos mostraram boa atividade sem efeito tóxico para célula hospedeira, além disso o composto 3a selecionado para o tratamento no ensaio in vivo de infecção com Leishmania amazonensis reduziu a lesão da orelha infectada, porém não reduziu a carga parasitária da orelha e do linfonodo drenante, além disso, o tratamento com o composto 3a não induziu alteração no peso do baço, nem alterações de alanino aminotransferase (ALT), aspartato aminotransferase (AST), creatinina e ureia. Compostos da série com substituintes 2-N,N’-dialquilamino-1,4-naftoquinona apresentaram atividade contra promastigotas de L.chagasi e L. amazonensis, com destaque para os derivados 1d, 1h e 1i que inibiram o crescimento de promastigotas de L. amazonensis acima de 50%, e os derivados 1d, 1e, 1f, 1h, 1k e 1n que exibiram pronunciada inibição do crescimento de promastigotas de L.chagasi, com mais de 70% de inibição. No ensaio contra as formas amastigotas de L.chagasi, os derivados 1a, 1b, 1c, 1d, 1h, 1i, 1k e 1m apresentaram significante atividade contra o crescimento das formas intracelulares do parasito. Os flavonoides SP1, SP2, SP3 e o extrato bruto de Solanum paladosum inibiram o crescimento de promastigotas de L. amazonensis e L. chagasi. Além disso, SP4 inibiu o crescimento de promastigotas de L. amazonensis. No que diz respeito à inibição do crescimento das formas intracelulares, SP1, SP3 e o extrato bruto foram estatisticamente significantes. Além disso, no ensaio in vivo de infecção com L. amazonensis os compostos SP1 e SP3 reduziram a carga parasitária da orelha infectado, porém não reduziram a carga parasitária do linfonodo. Na análise do ciclo celular da Leishmania, foi observado que SP1 e SP3 induziram mudança na fase S e G2/M do ciclo celular. Ademais, o composto SP3 na concentração de 100 μM induziu morte por apoptose e alterou a intensidade de autofagia, indicando atividade antiproliferativa. O composto 3,7,3',4'-tetra-O-methylquercetin (retusin) inibiu o crescimento de promastigotas e amastigotas de L.chagasi e L. amazonensis. No ensaio de infecção utilizando hamsters infectados com L. chagasi, o composto retusin diminuiu a carga parasitária no baço dos animais infectados. Entretanto, no ensaio in vivo de infecção de camundongos Balb/c com L. amazonensis, o composto retusin não reduziu a carga parasitária da orelha e do linfonodo drenante. Além disso, o ensaio de microscopia eletrônica de varredura revelou que o composto retusin induziu alterações morfológicas em promastigotas de L. chagasi. O composto retusin foi capaz de induzir morte por apoptose na concentração de 100 μM, provavelmente não dependente de caspases, além disso, inibiu topoisomerase de Leishmania. Os resultados indicam que os derivados 1,4-naftoquinonas e os compostos flavonoides de S. paladosum são ativos contra espécies de Leishmania, principalmente os compostos 1a, 1b, 1c, and 1m que foram ativos contra espécies de Leishmania nos ensaios in vitro, sem efeito deletério para célula hospedeira, e os flavonoides SP1, SP3 e retusin que foram ativos por via intraperitoneal no ensaio in vivo, indicando que estes são fortes candidatos a fármacos leishmanicidas.
37
TOMAZ, Alecsandra Ferreira. "Desenvolvimento de membrana de quitosana/1,4 naftoquinona para liberação controlada: curativo para feridas oncológicas." Universidade Federal de Campina Grande, 2017. http://dspace.sti.ufcg.edu.br:8080/jspui/handle/riufcg/320.
Full textAbstract:
Submitted by Lucienne Costa (lucienneferreira@ufcg.edu.br) on 2018-03-23T21:32:37Z
No. of bitstreams: 1
ALECSANDRA FERREIRA TOMAZ – TESE (PPGEP) 2017.pdf: 2915596 bytes, checksum: 50bc5abc5a322e77e912a5a1a69a3ce7 (MD5)Made available in DSpace on 2018-03-23T21:32:37Z (GMT). No. of bitstreams: 1 ALECSANDRA FERREIRA TOMAZ – TESE (PPGEP) 2017.pdf: 2915596 bytes, checksum: 50bc5abc5a322e77e912a5a1a69a3ce7 (MD5) Previous issue date: 2017-12-15
As lesões cutâneas associadas ao câncer de pele apresentam crescente importância na atualidade, visto que este tipo de câncer é o mais incidente para ambos os sexos no Brasil, mesmo sendo considerado de baixa letalidade. Suas características de sangramento, exsudação intensa e presença de odores, além da dificuldade da aceleração do processo cicatricial sugerem a necessidade do desenvolvimento de biomateriais que possam ser utilizados como curativos no intuito de prover melhor resposta à esta condição. Nesse sentido, esse trabalho teve como objetivo desenvolver membrana de quitosana para liberação controlada de 1,4-naftoquinona como proposta de curativo para feridas oncológicas. Para tanto, foram desenvolvidas membranas de quitosana e quitosana/1,4-naftoquinona pelo método de liofilização e evaporação de solvente (densas). Para quantificar o 1,4-naftoquinona nas membranas de quitosana foi utilizada a espectroscopia na região do ultravioleta (UV/VIS), cuja metodologia foi validada analíticamente. Para caracterização química, física e biológica destas foram utilizadas a Espectroscopia na Região do Infravermelho por Transformada de Fourier (FTIR), Difração de Raios X (DRX), Microscopia Eletrônica de Varredura (MEV), Termogravimetria (TG), Calorimetria Exploratória Diferencial (DSC), Ensaio de Tração, Teste de Molhabilidade, Grau de Intumescimento (GI), Biodegradação e Citotoxicidade. No ensaio de FTIR confirmou-se a reticulação e interação da quitosana com o 1,4-naftoquinona. Na técnica de DRX observou-se os picos característicos da quitosana nas membranas desenvolvidas e naquelas com 1,4-naftoquinona constatou-se um aumento da cristalinidade. Na MEV foram identificadas estruturas porosas, lamelares e fibrilares nas membranas liofilizadas e nas por evaporação de solvente uma estrutura lisa e homogêna. Os resultados de TG e DSC indicaram que a adição do agente reticulante e do 1,4-naftoquinona elevou à resistência à temperatura das amostras. As membranas por evaporação de solvente apresentaram maior resistência ao ensaio de tração. Todas membranas confeccionadas exibiram perfil de hidrofilicidade e GI elevado. Constatou-se que membranas densas degradaram mais que as liofilizadas. No ensaio de liberação controlada foi possível evidenciar uma liberação lenta, controlada, caracterizada em etapas. As membranas com melhores resultados no ensaio de liberação foram submetidas ao teste de citotoxicidade e apresentaram-se tóxicas. Conclui-se que essas membranas são promissoras para uso como curativo em liberação controlada de 1,4-naftoquinona.
Skin lesions associated with skin cancer present an increasing importance today, since this type of cancer is the most frequent for both sexes in Brazil, even though it is considered of low lethality. Its bleeding characteristics, intense exudation and the presence of odors, as well as the difficulty of accelerating the cicatricial process suggest the need for the development of biomaterials that can be used as curatives in order to provide better response to this condition. In this sense, this work aimed to develop a chitosan membrane for controlled release of 1,4-naphthoquinone as a curative proposal for oncological wounds. So, chitosan and chitosan/1,4-naphthoquinone membranes were developed by the freeze-drying and solution casting method (dense) method. To quantify the 1,4-naphthoquinone in the chitosan membranes, ultraviolet spectroscopy (UV/VIS) was used, whose methodology was validated analytically. For chemical, physical and biological characterization of these membranes, it was used Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), Traction Test, Wettability Test, Swelling Degree (SD), Biodegradation and Cytotoxicity. In the FTIR assay the cross-linking and interaction of chitosan with 1,4-naphthoquinone was confirmed. In the XRD technique the characteristic peaks of chitosan in the developed membranes were observed and in those with 1,4-naphthoquinone an increase in the crystallinity was observed. In the MEV, porous, lamellar and fibrillary structures were identified in the lyophilized membranes and in the solvent evaporation a smooth and homogeneous structure. The results of TG and DSC indicated that the addition of the crosslinking agent and 1,4-naphthoquinone increased the temperature resistance of the samples. The membranes by solvent evaporation presented higher resistance to the tensile test. All prepared membranes exhibited high hydrophilicity and SD profiles. Dense membranes have degraded more than lyophilized and the membranes submitted to the cytotoxicity assay were toxic. In the controlled release assay it was possible to demonstrate a slow, controlled release, characterized in steps. The membranes with the best results in the release assay were cytotoxic. It is concluded that such membranes are promising for use as dressing in controlled release of 1,4-naphthoquinone.
38
Brown, Jason David. "A Computational Investigation Into the Development of an Effective Therapeutic Against Organophosphorus Nerve Agent Exposure." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1416836502.
Full text
39
MELO, Valentina Nascimento e. "Síntese de 2-(1H-1,2,3-triazol)-1,4-naftoquinona de O-glicosídeos 2,3-insaturados com potencial antitumoral." Universidade Federal Rural de Pernambuco, 2015. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/6378.
Full textAbstract:
Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T15:25:59Z
No. of bitstreams: 1
Valentina Nascimento e Melo.pdf: 1846879 bytes, checksum: 0f435fbf6eac1935724bc84cb61e7e68 (MD5)Made available in DSpace on 2017-02-15T15:25:59Z (GMT). No. of bitstreams: 1 Valentina Nascimento e Melo.pdf: 1846879 bytes, checksum: 0f435fbf6eac1935724bc84cb61e7e68 (MD5) Previous issue date: 2015-03-16
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Two strategies were considered for the synthesis of 2,3-unsaturated O-glucosyl-1,2,3-triazoles. The reaction between tri-O-acetyl-D-glucal and triazole alcohols gave no stereoselectivity. In fact, β-isomer formation was increased. A second strategy furnished 2,3-unsaturated O-glucosides from tri-O-acetyl-D-glucal and alkynols via Ferrier rearrangement; this methodology employing montmorillonite K-10 doped with FeCl3∙6H2O affords new glycosides in good to excellent yields, short time and high α-stereoselectivity in dichloromethane. Subsequently, the glucosides were coupled with 2-azido-1,4-naphthoquinone to give a new series of 1,2,3-1H-triazolyl O-glucoside derivatives based on click reaction.
Duas estratégias foram consideradas para a síntese de 1,2,3-triazóis O-glicosídeos2,3-insaturados. A reação entre o tri-O-acetil-D-glucal e os alcoóis triazólicos não mostrou seletividade. De fato, a formação do isômero β foi aumentada. Uma segunda estratégia forneceu O-glicosídeos 2,3-insaturados a partir do tri-O-acetil-D-glucal e alquinóis via rearranjo de Ferrier; esta metodologia formou novos glicosídeos, empregando montmorilonite K-10 dopado com FeCl3∙6H2O em diclorometano, em rendimentos de bons à excelentes, baixo tempo reacional e alta α-estereosseletividade. Subsequentemente, os glicosídeos foram acoplados com 2-azido-1,4-naftoquinona formando uma nova série de derivados 1,2,3-1H-triazolil O-glicosídeos através da reação Click.
40
Bapela, MJ, N. Lall, JH Isaza-Martinez, T. Regnier, and JJM Meyer. "Variation in the content of naphthoquinones in seeds and seedlings of Euclea natalensis." South African Journal of Botany, 2008. http://encore.tut.ac.za/iii/cpro/DigitalItemViewPage.external?sp=1000789.
Full textAbstract:
A correlation between plant growth and accumulation of naphthoquinones (shinanolone
(1), 7-methyljuglone (2) and diospyrin (3)) was investigated in seeds and seedlings of
Euclea natalensis A.DC. In this study, the seeds represented the first stage whereas the
second seedling stage was defined as the stage, when the radicles were about 6 cm in
length. The lengths of the seedlings at the third, fourth and fifth seedling stages were
9 cm, 12 cm and 16 cm respectively. Plant materials collected from the five seedling
stages were separately extracted using chloroform and the naphthoquinones were then
quantified by means of High Performance Liquid Chromatography (HPLC). Shinanolone
(1), which was the only naphthoquinone detectible from seeds, accumulated at variable
rates (P < 0.01) and no trend could be established between its synthesis and seedling
growth. The content of shinanolone (1) ranged from 87.5 mg/kg in seeds (first stage) to a
high mean value of 1047 mg/kg during the fourth seedling stage. A significant correlation
(P < 0.01) was found between the mean concentrations of 7-methyljuglone (2) and
seedling growth. 7-Methyljuglone (2) was quantified at a high mean level of 5003 mg/kg
during the third seedling stage and was not detected from the seed samples. A positive
correlation (P < 0.01) was established between the concentration of diospyrin (3) and
seedling stages. Diospyrin (3) was detected at an elevated mean concentration of
6182 mg/kg during the fifth seedling stage, which was higher than the other quantified
naphthoquinones.
41
Gudmundsdóttir, Anna Dóra. "Photochemistry of some naphthoquinols in solid polymer matrices." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27471.
Full textAbstract:
The main objective of this work was to study how polymer media can modify the photochemical reactivity of dissolved guest molecules. Three tetrahydronaphthoquinols, whose photochemistry is known to be sensitive to the reaction medium, were synthesized for this study. The photochemistry of these compounds consisted of [2 + 2] cycloaddition in solution and hydrogen abstraction-initiated rearrangement in the solid state. Different photopro-ducts from solution and solid state photolysis were interpreted as being due to reaction from different conformers in the different media.
2,3,4aα,6,7,8aα-hexamethyl-4a,5,8,8a-tetrahydronaphthoquin- l-on-4β-ol, studied in poly(methyl methacrylate) and poly(vinyl acetate) films, was found to exhibit behavior that is intermediate to solution and solid state reactivity and is discontinuous at the glass transition temperature.
2,3,4aα,6,7,8aα-hexamethyl-4a,5,8,8a-tetrahydronaphthoquin-l-on-4α-ol, which was essentially unreactive in the solid state, was also studied. It was found to give the expected but not observed solid state product as the major product in poly(methyl methacrylate).
Finally, 2 , 3 ,4aα ,6,7, 8aα:-4a ,5,8, 8a- tetrahydronaphthoquin-1-on-4β-acetate was studied. As a result of differences in the local enviroment, this compound displayed unique photoreactivity in each of three different media: in solution it gave 5-exo-acetoxy-l,3,4,6,8,9-hexamethyltetracyclo [4.4.0.0[sup 3,9].0[sup 4,8]decan-2-one, in the pure crystalline phase it gave 5-exo-acetoxy-2-oxy-1,3,4,6,8,9-hexamethyltricyclo[4.4.0.0[sup 4,7]-dec-8-en -2-one and in poly(methyl methacrylate) films 5-exo-acetoxy-1,3,4,6,8,9-hexamethyltetracyclo[4.4.0.0[sup 3,7]dec-8-en-2-one, as a major product.
It has been demonstrated that polymer matrices are useful reaction media for reducing the rates of conformational interconversions to the point that alternative chemical processes that are normally too slow to be observed in solution become competitive. This leads to chemical consequences that in some cases mimic those observed in the solid state. In others, where crystals are unreactive for some reasons or where the crystal lattice can sterically impede certain reactions, new products can be formed.Science, Faculty of
Chemistry, Department of
Graduate
42
Chiwakata, M., la Mare Jo-Anne De, Adrienne Lesley Edkins, and Denzil R. Beukes. "Sarqaquinoic acid and related synthetic naphthoquinones inhibit the function of Hsp90." Georg Thieme Verlag KG, 2016. http://hdl.handle.net/10962/66324.
Full textAbstract:
publisher versionHeat shock protein 90 (Hsp90) is of critical importance in the proper folding of numerous proteins, including those involved in cancer. Consequently, there is significant interest in the discovery and development of Hsp90 inhibitors as anticancer drugs. In this study, we investigated the ability of sargaquinoic acid (SQA) and selected naphthoquinone derivatives to inhibit Hsp90 function. SQA was isolated and purified from Sargassum incisifolium while the naphthoquinones were synthesised via a straightforward sequence incorporating a Diels-Alder reaction between benzoquinone derivatives and myrcene followed by coupling with substituted alkyl or arylamines. Hsp90 inhibition was assessed by a client protein degradation assay. At a concentration of 1µM, SQA showed almost complete inhibition of Hsp90 but only moderate antiproliferative effects (IC50 658µM) against a Hs578T breast cancer carcinoma cell line. Interestingly, the most potent synthetic aminonaphthoquinone inhibited Hsp90 function by 50% at a concentration of 1µM but showed much improved activity against the Hs578T cell line (IC50 0.32µM). Furthermore, unlike geldanamycin, none of the compounds tested upregulates Hsp70 suggesting that these compounds may bind to the C-terminal end of Hsp90.
43
Teles, Aila Mirtes. "Contribuição farmacológica à gênese da inflamação neurogênica em vias aéreas de ratos frente a dois poluentes: Partículas eliminadas na exaustão do diesel (PED) e 1,2-naftoquinona (1,2-NQ)." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/42/42136/tde-24092007-094137/.
Full textAbstract:
Neste estudo efetuou-se uma análise comparativa da resposta inflamatória e estresse oxidativo produzido pela administração intratraqueal (i.tr.) das PED e/ou 1,2-NQ em vias aéreas de ratos. O efeito destes poluentes sobre a funcionabilidade dos macrófagos foi também avaliado. A injeção i.tr. das PED, numa dose incapaz de causar edema, promoveu efeito aditivo no edema e influxo de leucócitos induzido pela 1,2-NQ nas vias aéreas. O edema foi inibido por antagonistas de taquicininas ou capsaicina, mas o influxo de leucócitos não. O tratamento com estes poluentes aumentou a expressão gênica dos receptores TRPV1, taquicininas e TNFR1, as quais foram reduzidas, mas a iNOS aumentada, em animais depletados de neuropeptídeos. Concentrações elevadas de citocinas pró-inflamatórias foram encontradas no brônquio de ratos saudáveis e, mais intensamente, naqueles tratados com capsaicina. Níveis basais de 3-NT, IL-10 ou IFN-?? no brônquio não foram alterados pelos poluentes. A fagocitose de partículas de zimosan foi aumentada após a exposição de animais saudáveis e depletados de neuropeptídeos aos poluentes. A inflamação nas vias aéreas de ratos expostos ao MP do diesel é influenciada por concentrações de 1,2-NQ no ambiente, via mecanismo neurogênico.Pharmacological approaches on the healthy side effects evoked by the interaction between environmental pollutants are poorly studied. Here we tested the hypothesis that the environmental chemical 1,2-naphthoquinone (1,2-NQ) is implicated in the exacerbation of airways diseases induced by exposure to diesel exhaust particles (DEP), and that involves a neurogenic-mediated mechanism. Intra-tracheal (i.tr.) injection of DEP (1 and 5 mg/kg) or 1,2-NQ (35 and 100 nmol/kg) caused oedema in rat airways. DEP (at a dose unable to produce oedema) increased the 1,2-NQ-induced responses in the rat airways in a additive manner. This effect was reduced by L-732,138, an NK1 receptor antagonist, and in a lesser extent by the NK2 receptor SR48968. Capsaicin treatment also markedly reduced pollutants-induced oedema. Exposure to pollutants increased the TRPV1, NK1 and NK2 receptors gene expression in bronchus, an effect nearly abolished by capsaicin treatment. No evidence of increased 3-NT in main bronchus was found. Our results are consistent with the hypothesis that DEP-induced airways oedema is highly influenced by increased ambient levels of 1,2-NQ, and takes place by neurogenic-mediated mechanisms involving up-regulation of TRPV1 and tachykinin receptors.
44
Costa, Arinice de Menezes. "Estudo do mecanismo de aÃÃo citotÃxica de naftoquinonas sintÃticas anÃlogas do lapachol." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=11008.
Full textAbstract:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorFundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico
O lapachol, uma naftoquinona natural, e seus derivados sintÃticos tÃm demonstrado, nos Ãltimos anos, importantes aÃÃes citotÃxicas contra varias linhagens de cÃlulas tumorais, assim como significante atividade antitumoral contra alguns tumores. Assim, o objetivo desse trabalho foi avaliar o mecanismos de aÃÃo citotoxica em cÃlulas HL-60 de duas naftoquinonas sintÃticas anÃlogas do lapachol (compostos 1 e 2). Inicialmente foi investigado a atividade antiproliferativa dessas naftoquinonas apÃs um perÃodo de incubaÃÃo de 72h em cÃlulas leucÃmicas (HL-60) e cÃlulas mononucleadas do sangue perifÃrico (CMSP) onde foi observado que essas naftoquinonas mostraram-se ativas para estas linhagens com CI50 de 12 ÂM, 2,3 ÂM e 4,3 ÂM para o lapachol, composto 1 e composto 2, respectivamente em cÃlulas HL-60 e 13,7 ÂM e 34,0 ÂM para o composto 1 e 2 em cÃlulas CMSP, respectivamente. A atividade antiproliferativa em cÃlulas HL-60 apÃs 24 horas de incubaÃÃo foi avaliada com e sem co-tratamento com o antioxidante n-acetilcisteÃna (NAC). Assim, a CI50 sem NAC apÃs 24 horas de exposiÃÃo ao lapachol, composto 1 e composto 2 foi de 42,9 μM, 2,7 ÂM e 4,3 ÂM , respectivamente. JÃ CI50 com NAC (5 ÂM) apÃs 24 horas de exposiÃÃo ao lapachol, composto 1 e composto 2 foi de 180,0 μM, 46,0 ÂM e 18,0 ÂM , respectivamente. Estudos feitos em cÃlulas HL-60 indicaram que o lapachol e seus dois anÃlogos induzem morte celular por apoptose e necrose, como mostrado pelas mudanÃas morfolÃgicas avaliadas atravÃs do uso de coloraÃÃo May-GrÃnwald-Giemsa. Nos ensaios realisados por citometria de fluxo foi revelado que estes compostos promovem a geraÃÃo de espÃcies reativas de oxigÃnio (EROs) 18,86%, 13,31% e 39,11% respectivamente para o lapachol (82 ÂM) e compostos 1 e 2 (3,5 ÂM) e 40,94% e 60,49% para os compostos 1 e 2 (7,0 ÂM), respectivamente. O lapachol (82 ÂM) e os compostos 1 e 2 (3,5 ÂM) diminuÃram o nÃmero de cÃlulas com membrana Ãntegra 26,51%, 34,78% e 29,58% respectivamente e os compostos 1 e 2 (7,0 ÂM) diminuÃram 75,3% e 71,1%, respectivamente. A fragmentaÃÃo do DNA promovida por esses compostos foi observada a partir de 3 horas de exposiÃÃo sendo mais intensa apÃs 24 horas de exposiÃÃo aos compostos testados. O lapachol e os compostos 1 e 2 tambÃm promoveram a ativaÃÃo de caspases relacionadas com a via intrÃnseca de morte celular. AlÃm disso, mostraram induzir a quebra de fitas de DNA. Todos os efeitos citotÃxicos foram abolidos quando os compostos 1 e 2 foram co-incubados com o NAC, mostrando, dessa forma, a participaÃÃo de EROs na citotÃxicidade destas naftoquinonas.
The lapachol, one naphthoquinone natural, and its derivatives synthetic have demonstrated, in recent years, important actions cytotoxic against several lineages of tumor cells, well as signifier antitumoral activity against some tumors. Thus, the objective this work was to evaluate the mechanisms of action cytotoxic in cells HL-60 of two naphthoquinones synthetic analogous of lapachol (compounds 1 and 2). Initially was investigated at antiproliferative activity these naphthoquinones after a incubation period of 72 hours in leukemic cells (HL-60) and peripheral blood mononucleated cells (PBMC) where was observed that these naphthoquinones were active for these lines with IC50 of 12 ÂM , 2.3 ÂM and 4.3 ÂM for the lapachol, compound 1 and compound 2, respectively in cells HL-60 and 13.7 ÂM and 34.0 ÂM for compound 1 and 2 in cells PBMC, respectively. The antiproliferative activity in cells HL-60 after 24 hours incubation was evaluated with and without co-treatment with the antioxidant n-acetylcysteine (NAC). Thus, IC50 without NAC after 24 hours of exposure to lapachol, compound 1 and compound 2 was 42.9 ÂM, 2.7 ÂM and 4.3 ÂM, respectively. Have IC50 with NAC (5 ÂM) after 24 hours of exposure to lapachol, compound 1 and compound 2 was 180.0 ÂM, 46.0 ÂM and 18.0 ÂM, respectively. Studies done in HL-60 cells indicated that the lapachol and its two analogues induce cell death by apoptosis and necrosis, as shown by morphological changes evaluated through the use of staining May-GrÃnwald-Giemsa. In trials realisados by flow cytometry was revealed that these compounds promote the generation of reactive oxygen species (ROS) 18.86%, 13.31% and 39.11% respectively for the lapachol (82 ÂM) and compounds 1 and 2 (3,5 ÂM) and 40.94% and 60.49% for the compounds 1 and 2 (7.0 ÂM), respectively. The lapachol (82 ÂM) and the compounds 1 and 2 (3.5 ÂM) decreased the number of cells with intact membrane 26.51%, 34.78% and 29.58% respectively and the compounds 1 and 2 (7, 0 ÂM) decreased 75.3% and 71.1%, respectively. The DNA fragmentation promoted by such compounds was observed starting from 3 hours of exposure being more intense after 24 hours of exposure to tested compounds. The lapachol and the compounds 1 and 2 also promoted the activation of caspases related to intrinsic pathway of cell death. Furthermore, showed induce the synthesis of DNA strands. All cytotoxic effects were abolished when the compounds 1 and 2 were co-incubated with the NAC, showing thus the participation ROS in cytotoxicity these naphthoquinones.
45
Meye, Biyogo Alex. "Stratégie radicalaire SRN1/Mn(OAc)3 sur des dérivés naphtoquinoniques à visée pharmacologique." Electronic Thesis or Diss., Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4750.
Full textAbstract:
Ce travail est consacré à la recherche et au développement de nouvelles molécules à viséepharmacologique en série naphtoquinonique en utilisant des réactions par transfert monoélectroniquede type SRN1 et des cyclisations radicalaires oxydatives induites par l'acétate de manganèse(III). Lapremière partie décrit l’étude de la réactivité SRN1 de la 2-(chlorométhyl)-3-méthoxynaphtoquinoneavec divers anions nitronates conduisant à la formation de produits de C-alkylation avec de bonsrendements. Ces derniers ont fait l’objet d’une réaction de réduction-cyclisation permettant la synthèsede nouveaux dérivés benzo[g]indol-5(3H)-ones. Dans la seconde partie, une nouvelle réactiond’oxydation initiée par l’acétate de manganèse(III) a été développée sur la 2-hydroxy-3-méthylnaphtoquinone dans des conditions opératoires douces. En effet, la réactivité originale de la 2-hydroxy-3-méthylnaphtoquinone avec divers alcènes aromatiques en présence de Mn(OAc)3 et dedioxygène, a permis pour la première fois en série naphtoquinonique, l’obtention de nouveaux dérivésoriginaux dihydronaphto[2,3-c][1,2]dioxine-5,10(3H,10aH)-diones sous forme d’un mélange dediastéréoisomères à potentialités antipaludiques. Un mécanisme réactionnel original a été proposé pourla formation de ces produitsThis work is focused on the research and development of new pharmacologicalmolecules in naphthoquinonic series, synthesized by single electron transfer reaction SRN1 ormanganese(III) acetate catalyzed oxidative radical cyclization. The first part describes the SRN1reactivity of 2-(chloromethyl)-3-methoxynaphthoquinone with various nitronate anions leading to theC-alkylation products. The reduction-cyclization reaction of the latter derivatives allowed us to obtainnew benzo[g]indol-5(3H)-one derivatives. In the second part, a new reaction initiated by Mn(OAc)3 on2-hydroxy-3-methylnaphthoquinone was developed under mild conditions. Indeed, the original reaction of2-hydroxy-3-methylnaphthoquinone with various aromatic alkenes in presence of dioxygen led to newdihydronaphtho[2,3-c][1,2]dioxine-5,10(3H,10aH)-dione derivatives as a mixture of diastereoisomerswith antimalarial potential. An original mechanism was proposed in order to explain the formation ofthese products
46
Meye, Biyogo Alex. "Stratégie radicalaire SRN1/Mn(OAc)3 sur des dérivés naphtoquinoniques à visée pharmacologique." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4750.
Full textAbstract:
Ce travail est consacré à la recherche et au développement de nouvelles molécules à viséepharmacologique en série naphtoquinonique en utilisant des réactions par transfert monoélectroniquede type SRN1 et des cyclisations radicalaires oxydatives induites par l'acétate de manganèse(III). Lapremière partie décrit l’étude de la réactivité SRN1 de la 2-(chlorométhyl)-3-méthoxynaphtoquinoneavec divers anions nitronates conduisant à la formation de produits de C-alkylation avec de bonsrendements. Ces derniers ont fait l’objet d’une réaction de réduction-cyclisation permettant la synthèsede nouveaux dérivés benzo[g]indol-5(3H)-ones. Dans la seconde partie, une nouvelle réactiond’oxydation initiée par l’acétate de manganèse(III) a été développée sur la 2-hydroxy-3-méthylnaphtoquinone dans des conditions opératoires douces. En effet, la réactivité originale de la 2-hydroxy-3-méthylnaphtoquinone avec divers alcènes aromatiques en présence de Mn(OAc)3 et dedioxygène, a permis pour la première fois en série naphtoquinonique, l’obtention de nouveaux dérivésoriginaux dihydronaphto[2,3-c][1,2]dioxine-5,10(3H,10aH)-diones sous forme d’un mélange dediastéréoisomères à potentialités antipaludiques. Un mécanisme réactionnel original a été proposé pourla formation de ces produitsThis work is focused on the research and development of new pharmacologicalmolecules in naphthoquinonic series, synthesized by single electron transfer reaction SRN1 ormanganese(III) acetate catalyzed oxidative radical cyclization. The first part describes the SRN1reactivity of 2-(chloromethyl)-3-methoxynaphthoquinone with various nitronate anions leading to theC-alkylation products. The reduction-cyclization reaction of the latter derivatives allowed us to obtainnew benzo[g]indol-5(3H)-one derivatives. In the second part, a new reaction initiated by Mn(OAc)3 on2-hydroxy-3-methylnaphthoquinone was developed under mild conditions. Indeed, the original reaction of2-hydroxy-3-methylnaphthoquinone with various aromatic alkenes in presence of dioxygen led to newdihydronaphtho[2,3-c][1,2]dioxine-5,10(3H,10aH)-dione derivatives as a mixture of diastereoisomerswith antimalarial potential. An original mechanism was proposed in order to explain the formation ofthese products
47
Thaver, Veneesha. "Isolation and characterization of the cytotoxicity, intracellular bioactivity and mechanism of antimycobacterial action of Euclea natalensis-derived naphthoquinones." Thesis, University of Pretoria, 2010. http://hdl.handle.net/2263/31311.
Full textAbstract:
The major cause of HIV-related mortality in Sub-Saharan countries is pulmonary tuberculosis (TB), which is an escalating threat due to the emergence of multidrug resistant (MDR) and extremely multidrug resistant (XDR) TB. There is clearly an urgent requirement for the identification of novel, affordable anti-TB (as well as anti-HIV) drugs.
This study was undertaken with the objective of isolating and characterizing the antimycobacterial potential of 3 naphthoquinones, i.e. neodiospyrin, diospyrin and 7- methyljuglone present in the roots of Euclea natalensis. The laboratory research included: i) isolation of diospyrin and neodiospyrin, from the roots of E. natalensis; ii) assessment of the cytotoxicity of these agents and synthetic 7-methyljuglone for eukaryotic cells (Vero and THP-1 cells); iii) determination of the intracellular bioactivities of the naphthoquinones against the H37Rv strain of Mycobacterium tuberculosis (MTB); and iv) mechanistic studies designed to investigate the effects of the test agents on cation (K+/ Ca2+) fluxes and energy metabolism (ATP levels) in MTB and M. smegmatis.
With respect to the first objective, the naphthoquinones (diospyrin and neodiospyrin) were isolated from crude methanol extracts of crushed roots using chromatography and spectroscopic analysis. The yields of the compounds were 0.16 %, 0.32 %, and 0.12 % for neodiospyrin, diospyrin (isolated from plant) and synthetic 7-methyljuglone (synthesised in laboratory), respectively.
The effects of the compounds (0.3-50μg/ml) on the viability of Vero and THP-1 cells were measured using the XTT assay (sodium 3’-[1-(phenyl amino-carbonyl)-3, 4 tetrazolium]-bis-[4-methoxy-6-nitro] benzene sulfonic acid hydrate) based on cellular metabolic activity. All 3 test compounds were found to possess cytotoxic activity at 1.5- 12.5g/ml) for both cell lines.
Intracellular bioactivity of the test agents was measured using MTB-infected THP-1 cells as a surrogate for infected human macrophages. Following exposure of the MTBinfected cells to the test naphthoquinones, at a concentration range of 6.25-25g/ml, for 5 days, the cells were lysed and the viability of MTB in the lysates was then measured using the BACTEC radiometric system. All 3 test agents were found to be bioactive intracellularly, with complete inhibition of growth detected at 12.5, 25, and 6.25g/ml in the case of neodiospyrin, diospyrin, and synthetic 7-methyljuglone respectively.
The effects of the 3 naphthoquinones on mycobacterial cation fluxes were measured according to the magnitude of uptake of 86Rb+ (a surrogate for K+) and 45Ca2+, while ATP was measured using a chemiluminescence procedure. None of the test agents was found to affect Ca2+ uptake by the bacteria. However, all 3 test agents were found to be potent inhibitors of uptake of K+ by MTB and M. smegmatis, with inhibition detected at submicrogram concentrations of these agents. All 3 test agents, especially synthetic 7- methyljuglone, were found to interfere with energy metabolism in MTB, manifested as decreases in mycobacterial ATP levels.
Synthetic 7-methyljuglone which has the lowest MIC value for MTB (0.5μg/ml), and which was the most potent inhibitor of energy metabolism in MTB, shows promise as a potential anti-TB agent.These agents also are of potential value in drug modelling, possibly in the design of novel anti-TB agents which selectively target mycobacterial K+ transporters.Thesis (PhD)--University of Pretoria, 2010.
Immunology
Unrestricted
48
Bulovas, Arūnas. "Biomimetiniai (metil)naftochinono omega-merkapto darinių savitvarkiai monosluoksniai ant aukso ir sidabro paviršių: elektrocheminiai ir spektroskopiniai redokso virsmų ir struktūros tyrimai." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20100204_103017-67369.
Full textAbstract:
Sintezuotas didelis rinkinys naujų biomimetinių 1,4-naftochinono merkapto darinių, besiskiriančių šoninės grandinės ilgiu ir įterptomis funkcinėmis grupėmis. Jų savitvarkių monosluoksnių ant aukso ir sidabro paviršių struktūra ir redokso virsmai ištirti ciklinės voltamperometrijos ir paviršiaus sustiprintos Ramano spektroskopijos metodais. Ištirta monosluoksnio paviršinės koncentracijos ir kitų parametrų priklausomybė nuo modifikacinių tirpalų koncentracijos. Palyginti mišrūs 1,4-naftochinono darinių ir skirtingų alkantiolių, neturinčių redokso aktyvumo, monosluoksniai.A large set of biomimetic 1,4-naphthoquinone mercapto derivatives, varying in the side-chain length and intrachain functional groups, was synthesized. Structure and interfacial redox conversion of self-assembled monolayers on gold and silver surfaces, formed from newly synthesized compounds, were studied by cyclic voltammetry and surface-enhanced Raman spectroscopy. Low-density naphthoquinone-based monolayers were studied more thoroughly. Mixed monolayers of 1,4-naphthoquinone derivatives with different redox inactive alkylthiols were compared.
49
Neta, Maria Adalgiza dos Santos. "Atividade antifÃngica in vitro de compostos naftoquinoidais contra cepas de Candida tropicalis resistentes ao fluconazol." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9561.
Full textAbstract:
A incidÃncia de infecÃÃes oportunistas causadas por fungos, com destaque para as leveduras do gÃnero Candida vem aumentando substancialmente. Estudos relatam que tem sido observado um notÃvel crescimento de infecÃÃes por espÃcies nÃo albicans (Candida tropicalis, Candida glabrata, Candida parapsilosis e Candida krusei). Isolados clÃnicos resistentes aos azÃlicos, em especial ao fluconazol, sÃo cada vez mais relatados. As naftoquinonas sÃo uma importante classe de molÃculas biologicamente ativas, apresentando atividades antibacteriana, antifÃngica, antiviral, anti-inflamatÃria, antipirÃtica, anticancerÃgena e tripanocida e tem sido amplamente testadas em vÃrios estudos farmacolÃgicos. Nos Ãltimos anos intensificou-se o interesse nestas substÃncias, nÃo sà devido à sua importÃncia em processos bioquÃmicos vitais, como tambÃm ao destaque cada vez maior que apresentam em variados estudos farmacolÃgicos. O presente trabalho buscou avaliar e comparar o efeito antifÃngico de naftoquinonas frente a cepas de Candida tropicalis resistentes e sensÃveis ao fluconazol, utilizando diferentes tÃcnicas tais como mÃtodos de microdiluiÃÃo em caldo, procedimentos de citometria de fluxo e ensaio do Cometa. Utilizamos sete cepas de Candida tropicalis resistentes ao fluconazol para esse estudo, as quais foram isoladas de sangue e faziam parte da colecÃÃo de leveduras do LaboratÃrio de BioprospecÃÃo Experimental em leveduras (LABEL), afiliado com a Faculdade de FarmÃcia da Universidade Federal do Cearà . Foi utilizado trÃs compostos de naftoquinonas frente à 07 cepas de Candida tropicalis e foram submetidas aos testes de Sensibilidade in vitro , onde apresentaram uma potente atividade antifÃngica. AtravÃs da Citometria de Fluxo, foi possÃvel avaliar alteraÃÃes morfolÃgicas e de integridade da membrana significativas desses compostos frentes Ãs cepas, alÃm de disfunÃÃo mitocondrial e produÃÃo de espÃcies reativas de oxigÃnio. AtravÃs do ensaio do Cometa foi possÃvel encontrar danos significativos ao DNA. Em sÃntese, os resultados sugerem que estes compostos podem ser usados como agentes antifÃngicos para o tratamento de candidemiasThe incidence of opportunistic infections caused by fungi, with emphasis on Candida species has increased substantially. Studies report that there has been a notable increase of infections by non-albicans species (Candida tropicalis, Candida glabrata, Candida parapsilosis and Candida krusei). Clinical isolates resistant to azoles, particularly fluconazole, are increasingly reported. The naphthoquinones are an important class of active molecules biologically presenting antibacterial, antifungal, antiviral, antiinflammatory, antipyretic, anti-cancer and trypanocidal and has been tested extensively in several pharmacological studies. In recent years intensified the interest in in this substances, not only due to your importance in vital biochemical processes as well as the increasing emphasis that they show in various pharmacological studies. This study aimed to evaluate and compare the effect of antifungal naphthoquinones against strains of Candida tropicalis resistant and susceptible to fluconazole, using different techniques such as broth microdilution methods, procedures Flow Cytometry procedures and Comet assay. We use seven strains of Candida tropicalis resistant to fluconazole for this study, which were isolated from blood and were part of the collection of yeasts Experimental Laboratory Bioprospecting in yeast (LABEL), affiliated with the Faculty of Pharmacy, Federal University of CearÃ. We used three compounds of naphthoquinones against the seven strains of Candida tropicalis and were subjected to in vitro sensitivity tests, which showed an antifungal activity potent. Through Flow Cytometry, it was possible to assess morphological changes and membrane integrity of these compounds fronts to significant strains in addition to mitochondrial dysfunction and production of reactive oxygen species. Through the Comet assay was possible to find significant damage to DNA. In summary, the results suggest that these compounds may be used as antifungal agents for the treatment of candidemia
50
Júnior, Paulo Eliandro da Silva. "Estratégias de heterociclização aplicadas a produtos naturais e sintéticos subexplorados pela química medicinal." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/60/60138/tde-04062014-112413/.
Full textAbstract:
O presente trabalho divide-se em três capítulos: Capítulo I - Nova síntese de ?-xiloidona: rearranjo de Claisen em hidroxinaftoquinonas; Capítulo II - Síntese e estudo de reatividade de promissores núcleos heteroaromáticos subexplorados pela química medicinal; Capítulo III - Análise computacional de similaridade e propriedades físico-químicas dos núcleos heterocíclicos do capítulo II. O capítulo I descreve uma nova rota para a síntese de ?-xiloidona, um produto natural relacionado ao lapachol, subexplorado pela química medicinal. Esta rota é baseada no rearranjo propargílico de Claisen, a partir da reação de lausona com 3-cloro-3- metilbutino sob catálise de CuCl2/I2.Este capítulo também descreveu a síntese de um derivado furano naftoquinoidal, o qual pode ser utilizado como precursor de ?- duniona, via rearranjo de Claisen aril-alílico. Além da realização desta metodologia substituindo o 3-cloro-3-metilbutino por cinco diferentes alcinos. Este novo processo ofereceu como vantagens principais o menor custo dos catalisadores empregados, os rendimentos melhorados e o reduzido número de etapas reacionais em relação as rotas descritas na literatura para obtenção de?-xiloidona. O Capítulo II apresenta o desenvolvimento de métodos sintéticos novos e eficazes para 3 núcleos heterocíclicos (naftiridinona, pirazolopiridinona e dihidropirrolopirazinona) pouco explorados pela química medicinal porém com potencial para descoberta de fármacos. Buscando abranger metodologias orientadas pela diversidade, neste capítulo foi realizado um estudo preliminar de reatividade destes núcleos frente diferentes abordagens, tanto frente métodos diretos de arilação quanto metodologias clássicas de modificação de anéis aromáticos. Além disso, no capítulo III foram realizados estudos de similaridade para a obtenção de padrões estruturais que possam ser aplicados em programas de descoberta de fármacos assim como o estudo de propriedades físico-químicas dos núcleos do capítulo II. Todo este trabalho permitiu desenvolver 10 moléculas inéditas na literatura, bem como novas metodologias para a síntese de compostos previamente descritos.The present work is divided in two chapters: Chapter I - New synthesis of ? - xiloidone: Claisen rearrangement of hydroxynaphthoquinones; Chapter II - Synthesis and reactivity study of promising heteroaromatic coresunderstudied by medicinal chemistry; Chapter III - Similarity and physic-chemical properties analysis of the heterocyclic cores from chapter II. Chapter I describes a newsynthetic route to?- xiloidona, which isa natural product related to lapachol and understudied by medicinal chemistry. This route is based on propargyl Claisen rearrangement from the reaction of lawsone and 3-chloro-3- methylbutynemediated by CuCl2/I2. This chapter also describes the synthesis of a furan derivative which can be used as?- dunnione precursor. Also this methodology had been applied replacing the 3-chloro- 3-methyllbutynefor five different alkynes. This new process is associated with lower cost, improved yields and reduced number of reaction steps when compared to the literature. The chapter II aimed at the development of synthetic methods to obtain 3 heterocyclic cores(naphthyridinone, pyrazolopyridinoneand dihydropyrrolopyrazinone)with drug discovery potential but also understudied by medicinal chemistry. Diversity-oriented methodologies had been performedresulting in a reactivity study of these cores across severalsynthetic approaches. Furthermore, the chapter III described the similarity studies that were conducted aiming to obtain structural patterns that can be applied in drug discovery programs. This work describes the development of 10 non-published molecules as well as new methodologies for the synthesis of these previously described compounds.