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1
Abner, Erik 1986. "Identification of HIV-1 reactivating quinoline compounds as bromodomain inhibitors." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/565528.
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Tras la infección por VIH-1, el establecimiento de un depósito de células T en reposo infectadas latentemente con VIH impide la erradicación del virus en pacientes. Para lograr la erradicación, la terapia retroviral existente debe combinarse con medicamentos que reactiven los virus latentes. Previamente, nuestro grupo describió un nuevo compuesto químico, MMQO (8-metoxi-6-metilquinolin-4-ol) que es capaz de reactivar la transcripción viral a través de un mecanismo desconocido. El objetivo de este proyecto fue identificar los proteínas que interaccionan con MMQO e investigar su papel en la reactivación del VIH-1.
Hemos establecido que MMQO es capaz de inducir la transcripción de minigenomas provirales que carecen de genes para los componentes virales, lo que nos permite plantear la hipótesis de que el compuesto funciona principalmente a través de factores del huésped. La caracterización de los perfiles de transcripción de MMQO mediante microarrays de expresión nos permitió identificar numerosos rasgos provocados por el compuesto. MMQO muestra una robusta naturaleza inmunosupresora que afecta a la proliferación celular debido a la disminución de los niveles proteicos de cMyc y Bcl-2 y la desregulación de genes sensibles a acetilación. Estas características indican que MMQO imita las lisinas acetiladas de histonas y funciona como un inhibidor de bromodominio y dominio extraterminal (BET). Análisis adicionales de la expresión génica y proteómica confirmaron esta hipótesis y demostramos que MMQO desplaza de la cromatina a Brd4, un miembro de la familia BET y antagoniza el papel pro-latente de Brd4 cerca del sitio de inicio de la transcripción de VIH-1. Modelos computacionales de docking también confirmaron la especificidad de MMQO hacia los bromodominios de la familia BET y un ensayo in vitro mediante FRET contra los miembros de la familia, identificó que MMQO tiene una mayor afinidad hacia la proteína Brd9. Por último, hemos establecido que la inhibición de Brd9 tiene un mínimo efecto sobre la expresión proviral, lo que sugiere que la principal función de MMQO sobre VIH-1 se puede atribuir al desplazamiento de Brd4.
Debido a la amplia gama de propiedades de los inhibidores de la familia BET, estas moléculas se están evaluando actualmente en ensayos clínicos contra diversos tipos de cáncer y afecciones inmunitarias. MMQO, con un funcionamiento dual, es un nuevo miembro de esta clase de medicamentos. La estructura minimalista de MMQO puede ser muy prometedora ya que puede ser modificada para optimizar la afinidad hacia Brd9 / 4 y, potencialmente, podría ser de utilidad en la investigación contra una gran variedad de enfermedades, incluyendo el VIH.Upon HIV-1 infection, a reservoir of HIV latently infected resting T cells prevents the eradication of the virus from patients. To achieve eradication, the existing virus suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. Our group previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol), which is capable of reactivating viral transcription through an unknown mechanism. The objective of this project was to identify the molecular binding partners of MMQO and elaborate their role in the reactivation of HIV-1. We established that MMQO is capable of inducing HIV-1 independently of viral proteins by inducing transcription from proviral minigenomes lacking genes for viral components, allowing us to hypothesize that the compound primarily functions through host factors. Characterizing MMQO’s transcriptional profiles with total mRNA expression microarrays, we were able to identify numerous traits provoked by the drug. MMQO displayed a robust immunosuppressive nature, it affected cell proliferation by diminishing cMyc and Bcl-2 protein levels and increased the dysregulation of acetylation sensitive genes. These hallmarks indicated that MMQO mimics acetylated lysines of core histones and functions as a bromodomain and extraterminal domain (BET) protein family inhibitor. Further gene expression and proteomic analysis confirmed this supposition and we demonstrated that MMQO deposes of the BET family member Brd4 from global chromatin and antagonizes the pro-latent role of Brd4 near the transcription start site of HIV-1. Computational docking models also confirmed MMQO’s specificity towards the BET family bromodomains and an in vitro screening against the family members by FRET identified MMQO to have the highest affinity towards the Brd9 protein. Finally, we established that the inhibition of Brd9 had minimal effect on the proviral expression, suggesting that the primary function of MMQO on HIV-1 can be attributed to the displacement of Brd4. Due to the broad range of properties characteristic to BET family inhibitors, these molecules are currently being evaluated in clinical trials against various types of cancers and immune conditions. The dual functioning scaffold compound MMQO is a new member of this class of drugs. The minimalistic structure of MMQO shows promise for it to be further optimized for higher affinities towards Brd9 / 4 and could potentially be of use in research against a variety of diseases, including HIV.
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Pakade, Vusumzi Emmanuel. "Application of the Baylis-Hillman reaction in the preparation of quinoline derivatives." Thesis, Rhodes University, 2006. http://hdl.handle.net/10962/d1007669.
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The reaction of various 2-nitrobenzaldehyde derivatives with methyl vinyl ketone (MVK) in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) has afforded the Baylis-Hillman adducts in moderate to good yield. Dissolution of the catalyst in the solvent before the addition of the aldehyde was observed to improve the yield. Reduction of the Baylis-Hillman adducts was effected by catalytic hydrogenation using a 10% palladium-on- carbon catalyst in ethanol to give quinoline and quinoline-N-oxide derivatives and, in some cases, acyclic reduction products. All products were characterised using NMR and, where appropriate, HRMS methods. Selected quinoline-N-oxides were successfully converted to their corresponding quinoline derivatives using phosphorus tribromide (PBr₃) and DMF as solvent. Conjugate addition of the benzylamine and piperidine nucleophiles to the Baylis-Hillman adducts was also investigated but proved problematic, with one of the substrates undergoing a retro-Baylis-Hillman reaction to afford the aldehyde in ca. 40% yield, but seemingly only traces of the required product. Perkin-type coupling of two 2-methylquinolines with benzaldehyde was successfully effected to afford the desired styrylquinoline derivatives confirming the potential of the Baylis-Hillman approach to the construction of the analogues of known HIV-1 integrase inhibitors. Three ¹³C NMR chemical shift prediction programmes, viz., Chem Window, neural network and HOSE (hierarchically ordered spherical description of environment) methods were applied to selected representative compounds prepared in the project. The results from the three programmes correlated reasonably well with the experimental carbon-13 chemical shift data for each of the selected compounds.
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Harris, Tyler. "Photo-induced isomerization and dimerization of various styryl quinolines." View electronic thesis (PDF), 2009. http://dl.uncw.edu/etd/2009-2/harrist/tylerharris.pdf.
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Banini, Serge R. "Palladium-catalyzed syntheses of indoles, pyrroloindoles, quinolines a base-mediated formation of N-alkoxyindoles, and progress toward the first total synthesis of echinosulfone A /." Morgantown, W. Va. : [West Virginia University Libraries], 2008. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5710.
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Thesis (Ph. D.)--West Virginia University, 2008.Title from document title page. Document formatted into pages; contains xv, 275 p. : ill. Includes abstract. Includes bibliographical references (p. 107-113).
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Kaschula, Catherine Hart. "Haematin-Quinoline interactions and structure-activity relationships in the antimalarial chloroquine and related compounds." Doctoral thesis, University of Cape Town, 2002. http://hdl.handle.net/11427/6316.
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Includes bibliographical references.The nature of the ferriprotoporphyrin IX (Fe(III)PPIX) antimalarial drug target and its interactions with aminoquinolines was investigated spectrophotometrically. The antiquity of malaria, which is caused by protozoan parasites of the genus Plasmodium, is demonstrated by the host specificity of over 100 parasite species found in reptiles, birds and mammals. The four species of plasmodia that infect man are P. vivax, P. malariae, P. ovale and P. falciparum; of which P. falciparum is the most deadly (Bruce-Chwatt 1981 ).
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Evans, Alba Pilar. "New Ruthenium(II) Polypyridyl Compounds with Quinoline Type Ligands for the Treatment of Cutaneous Leishmaniasis." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511881725973833.
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Huang, Jinqing, and 黃普卿. "A study of the reaction mechanisms and reactive intermediates involved in halogenated compounds : trichloroethylene oxide, halogenated benzophenones, and halogenated quinoline-based phototriggers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208036.
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UV/Vis absorption spectroscopy (UV/Vis), femtosecond transient absorption spectroscopy (fs-TA), nanosecond transient absorption spectroscopy (ns-TA), and nanosecond time-resolved resonance Raman spectroscopy (ns-TR3), as well as density functional theory (DFT) computations were employed to study the mechanisms and the intermediates in reactions of selected halogenated compounds, including trichloroethylene oxide (TCE oxide), halogenated benzophenones (4-FBP, 4-ClBP, 4-BrBP, 3-FBP, 33’-DFBP, 3-ClBP, 3-BrBP, 2-FBP, 2-ClBP, and 2-BrBP), and halogenated quinoline-based phototriggers (BHQ-OPh and BHQ-OAc). This study investigated the halogen substituent effect on the mechanisms of various water-involved reactions and the influences from the number of halogens present, the type of halogen and the substituent position of the halogen in the molecules of interest. The general mechanisms for the reactions of these halogenated compounds were summarized along with discussion of the driving forces from the substituted halogen. First, TCE oxide was hydrolyzed to release chloride ions one by one which led to a complicated water-catalyzed decomposition. To account for the dehalogenation and the formation of CO with three kinds of carboxylic acids (formic acid, glyoxylic acid, and dichloroacetic acid), the predominant decomposition pathways were examined by comparing the computed activation energies for the formation of different products. From these comparisons, the ring-opening reaction was identified as the rate-determining step, which is also supported by previous experimental observations reported in the literature. Based on all of these analyses, the mechanisms of the water-catalyzed decomposition reactions were determined and a water-assisted HCl elimination model has been proposed. Second, some halogen-substituted benzophenones demonstrated an efficiency for a photosubstitution reaction and the related photohydration reactions. Interestingly, the efficient photosubstitution reactions of 3-FBP and 33’-DFBP were dependent on the solution acidity and reached a maximum in 1 M HClO4 CH3CN/H2O (1/1) solution. Only the photohydration reaction took place for the 3-ClBP, 3-BrBP, 4-FBP, 4-ClBP, and 4-BrBP molecules. Nevertheless, no special photochemical reaction occurred for 2-FBP, 2-ClBP, and 2-BrBP. The mechanisms and intermediates were directly characterized by spectroscopic observations and rationalized by results from DFT computations. According to these results, the general mechanisms for the photosubstitution reaction and the related photohydration reactions of halogenated benzophenone derivatives were summarized. These results reveal that the efficiency in forming the corresponding hydroxy benzophenone is influenced by the solution acidity, substituent positions, and the character of the substituted halogens. The substituted halogen is the driving force of this photosubstitution reaction. This conclusion provides insight into several possible applications that are also briefly discussed in this thesis. Lastly, the BHQ-OPh system was found to undergo an extraordinary efficient excited-state proton transfer (ESPT) to initiate a dehalogenation reaction. The fs-TA and ns-TA spectra indicate clearly the interactions between four prototropic forms of BHQ-OPh, which were characterized by UV-Vis spectra under different pH values. These prototropic forms play important roles in inducing further dehalogenation, thus their structural configurations were also investigated by DFT computations. Besides, competing with the dehalogenation reaction, BHQ-OAc underwent another photodeprotection to release the OAc group. The comparison between BHQ-OPh and BHQ-OAc provides further information in understanding the mechanisms of dehalogenation reactions and photodeprotection reactions of these quinoline-based phototriggers.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
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Vezmar, Marko. "Pharmacological effects of quinoline-related compounds in human tumour cells overexpressing the multidrug resistance protein (MRP)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0003/MQ37175.pdf.
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Tittle, James Alfred. "Ab Initio Studies of High Temperature Pyrolysis Mechanisms in Heterocyclic Nitrogen-Containing Compounds." Digital Commons @ East Tennessee State University, 2000. https://dc.etsu.edu/etd/21.
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The decomposition mechanisms of various coal constituents undergoing pyrolysis are of great concern in environmental circles (especially those coal constituents containing nitrogen). Most methods of burning coal that are efficient involve doing so at high temperatures. This invariably results in a large portion of non-combusting coal being heated to high temperatures also causing pyrolysis of the original coal constituents. The end result of such pyrolysis is the production of a number of noxious gaseous products. If we are to design methods of reducing the amount of toxins that are produced from the industrial use of coal, it is necessary to understand the pyrolysis process mechanistically. Due to the great number of coal constituents, a reasonable approach to such a mechanistic study is to use a simpler model. Pyridine makes an excellent starting model upon which to build. Our study focuses on interpretation of proposed reaction channels from experimental work on pyridine, quinoline and isoquinoline shock-tube decomposition in light of new ab initio energy calculations using Gaussian 98. The pathways thus determined support the proposed pyrolysis mechanisms and agree with experimental evidence obtained from independent groups of researchers performing shock tube pyrolysis.
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Gibhard, Liezl. "The effect of Pheroid™ technology on the bioavailability of quinoline-based anti-malarial compounds in primates." Thesis, North-West University, 2012. http://hdl.handle.net/10394/9025.
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Resistance against anti-malarial drugs remains one of the greatest obstacles to the effective control of malaria. The current first-line treatment regimen for uncomplicated P.falciparum malaria is based on artemisinin combination therapies (ACTs). However, reports of an increase in tolerance of the malaria parasite to artemisinins used in ACTs have alarmed the malaria community. The spread of artemisinin-resistant parasites would impact negatively on malaria control.
Chloroquine and amodiaquine are 4-aminoquinolines. Chloroquine and amodiaquine were evaluated in a primate model by comparing the bioavailability of these compounds in a reference formulation and also in a Pheroid® formulation. In vivo pharmacokinetic studies were conducted for chloroquine, and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies were conducted for amodiaquine. Pheroid® technology forms the basis of a colloidal drug delivery system, and it is the potential application of this technology in combination with the 4-aminoquinolines that was the focus of this thesis. Pheroid® is a registered trademark but for ease of reading will be referred to as pheroid(s) or pro-pheroid(s) throughout the rest of the thesis.
The non-human primate model used for evaluation of the pharmacokinetic parameters was the vervet monkey (Chlorocebus aethiops). Chloroquine was administered orally at 20 mg/kg. A sensitive and selective LC-MS/MS method was developed to analyze the concentration of chloroquine in both whole blood and plasma samples. The Cmax obtained for whole blood was 1039 ± 251.04 ng/mL for the unformulated reference sample of chloroquine and 1753.6 ± 382.8 ng/mL for the pheroid formulation. The AUC0-inf was 37365 ± 6383 ng.h/mL (reference) and 52047 ± 11210 ng.h/mL (pheroid). The results indicate that the use of pheroid technology enhances the absorption of chloroquine. The effect of pheroid technology on the bioavailability of amodiaquine and N-desethylamodiaquine was determined in two groups of vervet monkeys, with the reference group receiving capsules containing the hydrochloride salt of amodiaquine and the test group receiving capsules containing a pro-pheroid formulation of amodiaquine. Amodiaquine was administered at 60 mg/kg. Blood concentrations of amodiaquine and N-desethylamodiaquine samples were monitored over 13 time points from 0.5 to 168 hours. Amodiaquine and pro-pheroid formulated amodiaquine were incubated in vitro with human and monkey liver (HLM and MLM) and intestinal (HIM and MIM) microsomes and recombinant cytochrome P450 enzymes. The in vitro metabolism studies confirm the rapid metabolism of amodiaquine to the main metabolite N-desethylamodiaquine in monkeys. Although the pharmacokinetic parameters varied greatly, parameters for both the parent compound and main metabolite were lower in the test formulation compared to the reference formulation. For HLM, MLM and CYP2C8, the pro-pheroid test formulation showed significantly longer amodiaquine clearance and slower formation of N-desethylamodiaquine. However, the effect was reversed in MIM.
Pheroid technology impacts differently on the bioavailability of the various pharmaceutical classes of anti-malarials. Pheroid technology did not enhance the bioavailability of amodiaquine or N-desethylamodiaquine. This is contrary to the observed effects of pheroid technology on the pharmacokinetics of other drugs such as artemisone and chloroquine where it increases the area under the curve and prolongs the drug half-life.Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
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Murray, Lorna. "New gas-phase cascade reactions of stabilising phosphorus ylides leading to ring-fused indoles and quinolines." Thesis, University of St Andrews, 2010. http://hdl.handle.net/10023/971.
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Synthesis and flash vacuum pyrolysis (FVP) of stabilised phosphorus ylides containing an o-amino functionalised benzene ring has been examined for the first time. Model studies using N-methyl-N-tosyl and N-mesyl-N-methyl ylides showed that the ylides could be prepared, although yields were variable, and had the expected spectroscopic properties. Upon FVP, however, the expected loss of Ph₃PO and the sulfonyl group was accompanied by unexpected transfer of the reactive site from nitrogen to carbon giving 3- substituted quinolines rather than the expected indole products. Moving to ylides with an α-cinnamoyl group (or heterocyclic analogue) did, however, result in the originally planned tandem cyclisation leading to ring-fused carbazole products. N-Benzyl was also found to be a suitable thermally labile group and a series of α-cinnamoyl N-benzyl-N-methyl ylides were prepared and characterised. For their synthesis, use of N-cinnamoylbenzotriazoles was found to be preferable to cinnamoyl chloride, requiring only half the amount of amino-functionalised phosphonium salt. While FVP of some of these ylides led to benzo-, furo- and thienocarbazoles in good yield, others again gave quinoline-type products pointing to a fine balance between the two alternative modes of cyclisation. It was noted that one of the furocarbazole products was very similar to a natural product, Eustifoline D, isolated from the medicinally active shrub Murraya euchrestifolia from Taiwan and its synthesis was planned. With a view to producing the required N-H carbazole, N,N-dibenzylamino amino ylides were prepared and were found to exhibit restricted rotation leading to broad NMR signals. Their FVP again led to both quinoline and carbazole products, with the former having usually, but not always, lost a phenyl group. Mechanistic pathways for the formation of the various products are proposed. Complete assignment of the complex ¹H NMR spectra of the various fused-ring heterocyclic products was achieved, assisted by simulations in many cases. The ylide precursor required for Eustifoline D was prepared in five steps and 10% overall yield from 5-methylanthranilic acid. The final FVP step gave a quinoline as the major product, but the minor product was Eustifoline D, spectroscopically identical to the natural product.
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Liebman, Katherine May. "New 4-Aminoquinoline Compounds to Reverse Drug Resistance in P. falciparum Malaria, and a Survey of Early European Antimalarial Treatments." PDXScholar, 2014. http://pdxscholar.library.pdx.edu/open_access_etds/2114.
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Intermittent fevers caused by Plasmodium parasites have been known for millennia, and have caused untold human suffering. Today, millions of people are afflicted by malaria each year, and hundreds of thousands die. Historically, the most successful synthetic antimalarial drug was chloroquine, as it was safe, inexpensive, and highly efficacious. However, plasmodial resistance to chloroquine now greatly limits its utility. Previously in our laboratories it has been shown that attachment of a "reversal agent moiety" to the side chain of chloroquine can result in the restoration of activity against chloroquine-resistant strains of P. falciparum malaria. In the first part of the work presented here, a study has been made of the importance of the quinoline ring substitution pattern to the activity of such reversed chloroquines. The compounds presented here include those bearing a substituent in the 2-, 5, 6-, 7-, and/or 8- position, and include those with chloro, bromo, iodo, fluoro, nitro, trifluoromethyl, methyl, and methoxy substituents. For reversed chloroquines, 2-, 5-, and 8- substituents have been found to decrease in vitro antiplasmodial activity against P. falciparum relative to 7-chloro substitution, whereas 6- and 7- substituted compounds with various substituents have in many cases similar activity to that of 7-chloro substituted compounds. Little difference has been observed between 6- and 7- substitution, or between chlorine and a methyl group in position 6. In most cases these effects on activity are directionally similar to those observed for chloroquine analogs without an attached reversal agent, but the magnitude of the effect is generally smaller, suggesting that the activities of reversed chloroquines are less affected by modifications to the quinoline ring system than is true for chloroquine analogs without an attached reversal agent.
The second portion of this work presents an asymmetrical bis-quinoline (PL241) that is highly active against P. falciparum malaria, with an IC50 of less than 0.1 nM for all strains tested. Mechanistic studies have been performed in which the substitution patterns of the two quinoline rings of PL241 are modified in ways that indicate that either ring system is equally capable of participating in the antimalarial activity of these compounds. The excellent in vitro antiplasmodial activity of PL241 makes this a compound of great interest for further development as a potential antimalarial drug.
In the third part of this work, a survey has been made of antimalarial treatments recommended in the European medical literature from the time of Pliny the Elder (active in the first century A.D.) through the advent of modern malaria chemotherapy in the early twentieth century. In the fifteen primary sources utilized in this study, 251 distinct substances - primarily plants - were identified as having likely been used in the treatment of malaria. Of the 38 substances that were described in three or more sources, at least fifteen have been examined by other workers for antiplasmodial activity; in many cases, they were found to have antiplasmodial activity in vitro or in vivo. However, the majority of the phytotherapies for malaria identified in this project have not yet been tested against Plasmodium species, and may provide valuable leads in the search for new compounds active against drug-resistant malaria.
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Ferreira, Maria Eugênia de Oliveira. "Adsorção de compostos nitrogenados utilizando carvão ativado." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/8749.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Heavy petroleum fractions, especially the vacuum residue, concentrate the largest amounts of nitrogen compounds. Such compounds are considered contaminants of the refining process, and interfere in the conversion steps to obtain lighter derivatives from the heavy fractions. In this study, the aim was to evaluate the removal of nitrogen compounds by adsorption process. Quinoline solution solubilized in toluene was used as a synthetic filler. Commercial activated carbons from coconut shell of babaçu and dendê in their original form and chemically modified with concentrated solutions of nitric and sulfuric acid, as well as sulfonated carbon developed from the rice husk, were evaluated for the adsorption capacity against compounds nitrogen residues present in the vacuum residue and synthetic charge. The textural characteristics of the adsorbents were also evaluated, in which it was observed that the modification with acid reduces the specific area of the activated carbons, but it promotes an increase in the removal of quinoline from the medium. From the preliminary batch adsorption test, the activated carbon from dendê treated with sulfuric acid (CDAS) was able to remove 67.08% of the quinoline present in the solution and was selected for kinetic and equilibrium study. The adsorption kinetics of quinoline were relatively fast for the three concentrations studied (500, 2000, 5000 mg L-1), reaching equilibrium after 240, 120 and 60 minutes of contact, respectively. The kinetic data for the three systems fit the pseudo-second order model better. The equilibrium data were better adjusted to the Freundlich model, revealing the physisorption character of adsorptive process. The maximum adsorption capacity obtained by Langmuir model was 56.63 mg g-1. The results show that CDAS is a promising adsorbent for the removal of quinoline in organic medium. In relation to the vacuum residue sample, batch adsorption tests were conducted in such a way to ascertain the efficiency in class N removal. The results of Mass Spectrometry, ESI (±) Orbitrap MS, showed that the adsorbents CBB and CBAN were more selective in the removal of the non-basic nitrogen compounds, while the basic nitrogenous ones were more persistent and were not removed by any of the adsorbents tested.
As frações pesadas do petróleo, especialmente o resíduo de vácuo, concentram as maiores quantidades de compostos nitrogenados. Tais compostos são considerados contaminantes do processo de refino, e interferem nas etapas de conversão para obtenção de derivados mais leves a partir das frações pesadas. Esta dissertação teve por objetivo avaliar a remoção de compostos nitrogenados por meio do processo de adsorção. Solução de quinolina solubilizada em tolueno foi utilizada como carga sintética. Carvões ativados comerciais de casca de coco de babaçu e de dendê, em suas formas original e modificados quimicamente com soluções concentradas de ácido nítrico e sulfúrico, além de carvão sulfonado desenvolvido a partir da casca de arroz, foram avaliados quanto à capacidade de adsorção frente a compostos nitrogenados presentes na carga sintética e no resíduo de vácuo (resíduo da última etapa de destilação do petróleo). As características texturais dos adsorventes também foram avaliadas, e foi observado que a modificação com ácido reduziu a área específica dos carvões, no entanto promoveu o aumento da remoção de quinolina do meio. A partir do teste preliminar de adsorção em batelada, o emprego do carvão ativado da casca de dendê tratado com ácido sulfúrico (CDAS) resultou na remoção de 67,08% da quinolina presente na solução e foi selecionado para estudo cinético e de equilíbrio. A cinética de adsorção da quinolina revelou um processo relativamente rápido para as três concentrações estudadas (500, 2000, 5000 mg L-1), atingindo o equilíbrio após 240, 120 e 60 minutos de contato, respectivamente. Os dados cinéticos, para os três sistemas, foram ajustados com sucesso ao modelo de pseudo-segunda ordem. Os dados de equilíbrio foram melhor ajustados ao modelo de Freundlich, revelando o caráter de fisissorção do processo adsortivo. A capacidade de adsorção máxima, obtida segundo modelo de Langmuir foi de 56,63 mg g-1. Os resultados mostram que o CDAS é um adsorvente promissor para a remoção de quinolina em meio orgânico. Em relação à amostra de resíduo de vácuo, ensaios de adsorção em batelada foram conduzidos de tal forma a averiguar a eficiência na remoção da classe N. Os resultados de Espectrometria de Massas, ESI (±) Orbitrap MS, mostraram que os adsorventes CBB e CBAN foram mais seletivos na remoção dos compostos nitrogenados não-básicos, enquanto os nitrogenados básicos mostraram-se mais persistentes, não sendo removidos por nenhum dos adsorventes testados.
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Tukulula, Matshawandile. "The design and synthesis of novel HIV-1 protease inhibitors." Thesis, Rhodes University, 2009. http://eprints.ru.ac.za/1563/.
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Fantin, Creusa Aparecida. "Síntese e caracterização dos compostos de adição entre os mono e dicloroacetatos de lantanídeos (III) e a quinolina-N-óxido (QNO)." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/46/46134/tde-14032018-115520/.
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Este trabalho descreve a síntese e caracterização dos compostos de adição obtidos pela reação entre os monocloroacetatos (CA) e dicloroacetatos (DCA) de lantanídeos (III) com a quinolina-N-óxido (QNO), na presença de etanol e ortoformiato de trietila. Os compostos foram obtidos na forma sólida e caracterizados por análise elementar, testes de solubilidade, medidas de condutância eletrolítica, difração de raios X (método do pó), espectros de absorção na região do infravermelho, espectros de absorção na região do visível dos compostos de Nd, espectros de emissão dos compostos de Eu e análise térmica. Os experimentos de análise térmica permitiram estudar o comportamento térmico dos compostos. A associação dos resultados de análise elementar e termogravimétrica permitiu sugerir as seguintes fórmulas mínimas: a) Ln(DCA)3.yQNO.wEtOH onde, y = w = 8/9 para Ln= La; y = w = 1 para Ln= Ce; y = 1 e w =¾ para Ln= Pr, Nd e Sm; y = 1 e w = O para Ln= Eu ao Lu e Y. b) Ln(CA)3.QNO, onde Ln= La ao Ho e Y. Os compostos não são higroscópicos, e possuem coloração bege, em sua grande maioria. São solúveis em DMF, DMSO, HMPA e água, e insolúveis em hexano, ciclohexano, dimetoxipropano, benzeno, clorofórmio, cloreto de metileno, tolueno, acetonitrila e acetona. As medidas de condutância, em solução de DMF, revelaram que os compostos se comportam como não eletrólitos, indicando que os ânions CA e DCA estão coordenados ao íon Ln3+. Os difratogramas de raios X ( método do pó) mostraram que os compostos de adição de dicloroacetatos possuem três séries isomorfas. Os espectros de absorção no infravermelho indicaram que a coordenção da QNO e dos ânions CA e DCA ocorre através do átomo de oxigênio, mas não permitiram evidenciar a coordenção do EtOH nos compostos de adição de dicloroacetatos, porém os resultados de análise térmica confirmaram a presença do etanol para os compostos de La ao Sm. As associações das técnicas auxiliaram na definição da estequiometria e existência das séries isomorfas. Os espectros de absorção dos compostos de Nd mostraram que as interações Nd3+- ligantes são de caráter eletrostático. Baseando-se nas transições 4I9/2 → 4G5/2, 2G7/2 foi possível determinar o parâmetro nefelauxético [β = 0,990 (CA) e β = 0,993 (DCA)], o fator de covalência [b1/2 = 0,070 (CA) e b1/2 = 0,0502 (DCA)] e o parâmetro de Sinha [δ = 1,01 (CA) e δ = 0,705 (DCA)]. Os espectros de emissão dos compostos de Eu, registrados a 77 K, sugeriram a simetria C3v para o composto de Eu(CA)3.QNO e C2v para o composto Eu(DCA)3.QNO. As curvas termoanalíticas evidenciaram que o processo de decomposição térmica ocorre em multi-etapas e que o produto final é o respectivo óxido.This work describes the synthesis and characterization of the addition compounds obtained between lanthanide (III) mono and dichloroacetates with Quinoline-N-oxide (QNO) in the presence of ethanol and triethyl orthoformate. These compounds were obtained in the solid form and characterized by elemental analysis, solubility tests, electrolytic condutance measures, X-ray diffraction (powder method), infrared absorption spectroscopy, visible absorption spectroscopy of the Nd compounds, emission spectroscopy of the Eu compounds and thermal analysis. The thermal analysis experiments allowed studying the thermal behavior of the compounds. The association of the results of elemental analysis and thermogravimetry allowed to suggest the minimum formule: a) Ln(DCA)3.yQNO.wEtOH, where y = w = 8/9 when Ln = La; y = w = 1 when Ln = Ce; y = 1 and w = 3/4 when Ln = Pr, Nd and Sm; y = 1 and w = 0 when Ln = Eu to Lu and Y. b) Ln(CA)3.QNO, where Ln= La -Ho e Y. The compounds are not hygroscopic and are beige coloration. They are soluble in DMF, DMSO, HMPA and water, but they are insoluble in hexane, ciclohexane, dimetoxipropane, benzene, chloroform, methylene chloride, toluene, acetonitrile and acetone. In DMF solution, the conductance measurements revealed that the compouds behave as non-electrolytes, indicating that CA and DCA ions are coordinated to the ion Ln3+. X-ray patterns suggest that the addition compounds of dichloroacetates and monochloroacetates have, respectively, three and four isomorphous series. The infrared spectra indicated that ligand and anions coordination to Ln3+ occurs through the oxygen atom, but they did not confirm the EtOH coordination in the addition compounds of dichloroacetates, however the results of thermal analysis confirmed the alcohol presence in the La to Sm complexes. The techniques association support in stoichiometry definition and isomorphic series. The absorption spectra of the Nd compounds suggest that the Nd3+-ligand interactions are of electrostatic character. Based in the 4I9/2 → 4G5/2, 2G5/2 transitions was possible to determine the spectroscopic parameters: nephelauxetic parameter [β = 0,990 (CA) and β = 0,993 (DCA)], covalency factor [bl/2 = 0,070 (CA) and b1/2 = 0,0502 (DCA)] and Sinha\'s parameter [δ = 1,01 (CA) and δ = 0,705 (DCA)]. The emission spectra of the Eu compounds, at 77 K, suggest that the symmetry for the Eu3+ ions is C3v for Eu(CA)3.QNO and C2v for Eu(DCA)3.QNO. The thermoanalytical curves evidenced that the thermal decomposition process occurs in multi-stages and that the final product is the respective oxide.
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Lee, Yi-Chen. "Studies towards the development of novel HIV-1 integrase inhibitors." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1005022.
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The project has focused on the preparation of several series of compounds designed as potential HIV-1 integrase inhibitors. Various 2-nitrobenzaldehydes have been reacted with two activated alkenes, methyl vinyl ketone (MVK) and methyl acrylate, under Baylis-Hillman conditions to afford α-methylene-β-hydroxylalkyl derivatives in moderate to excellent yields. The reactions were conducted using the tertiary amine catalysts, 1,4-diazabicyclo[2.2.2]octane(DABCO) or 3-hydroxyquinuclidine (3-HQ) with chloroform as solvent, and yields were optimised by varying the catalyst, reagent concentrations and the reaction time. Reductive cyclization of the Baylis-Hillman adducts via catalytic hydrogenation, using 10% palladiumon-carbon catalyst in ethanol, afforded quinoline and quinoline N-oxide derivatives. In some cases “acyclic” reduction products were also isolated. Reaction of the Baylis-Hillman MVK adducts with HCl, has resulted in effective nucleophilic (SN’) displacement of the hydroxyl group to afford allylic chloride derivatives. Direct substitution of these chloro derivatives by secondary or primary amines, followed by catalytic hydrogenation gave quinoline derivatives containing a 3-aminomethyl substituent. The Baylis-Hillman ester adducts obtained from reaction with methyl acrylate were treated directly with various amines to give diastereomeric conjugate addition products. Reactions with piperazine gave N,N’-disubstituted piperazine products. The piperidine derivatives have been dehydrated to give cinnamate esters in moderate yields. The products, which have all been satisfactorily characterised by elemental (HRMS) and spectroscopic (1- and 2-D NMR) analysis, constitute a “library” of compounds for in silico and in vitro studies as potential HIV integrase inhibitors.
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Tran, Christine. "Développement de sondes activables à deux photons pour une utilisation en neurosciences." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB165.
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Des sondes photoactivables (composés “cagés”) dérivées de la 2-hydroxyméthylène-diméthylaminoquinoléine, ont été préparées et testées pour une application en neurophysiologie. Ces sondes montrent une stabilité hydrolytique élevée et une faible fluorescence, avec des cinétiques de photofragmentation rapides sous irradiation UV (365 nm). Il en est également de même dans des conditions biphotoniques en IR proche (730 nm). Une optimisation de cette plateforme a été réalisée en modifiant la nature et la position des substituants du chromophore, en augmentant la conjugaison et en incorporant des éléments de symétrie C2 et S3, conduisant aux sondes dipolaires, quadrupolaires (dimériques) et octupolaires (trimériques) à haute sensibilité biphotonique ( < 2,50 GM). Les dérivés les plus efficaces ont été testés dans des expériences en neurophysiologie. Tandis que les dérivés de kaïnate sont suffisamment stables en solution aqueuse à pH 7,4 pour les expériences en conditions physiologiques, les dérivés de L-glutamate et GABA ont nécessité une connexion de type carbamate avec la plateforme photoactivable. Sans irradiation, les solutions « stock » de ces composés « cagés » (c = 200-300 µM) n’ont pas produit d’effets majeurs sur l'excitabilité des neurones à en juger par le manque d'effet sur l'activité neuronale ou de potentiels d’actions synaptiques spontanés provoqués par une dépolarisation. La photolyse en lumière blanche par pulses courts d’irradiation a permis la libération de substances actives en quantité suffisante pour produire de grands courants (jusqu’à 5 nA) dans les neurones de PurkinjePhotosensitive molecular probes (‘caged’ compounds) derived from 2-hydroxymethylenedimethylaminoquinoline were prepared and tested for applications in neurophysiology. These compounds show high hydrolytic stability and low fluorescence, with fast fragmentation kinetics upon UV irradiation (365 nm), and under two photon photolysis conditions (730 nm). This platform was optimized by modifying the substitution pattern, increasing the conjugation length and incorporating C2 or S3 symmetry elements. Dipolar, quadrupolar (dimer) and octupolar (trimer) derivatives were thus synthesized and were found exhibiting high two-photon sensitivity ( < 2,50 GM). The most efficient probes were tested in neurophysiological experiments. While kaïnate derivatives are stable in aqueous solution at pH 7.4 in physiological conditions, L-glutamate and GABA derivatives required the use of a carbamate linker. Without irradiation, any major changes were observed on neuron excitability with “stock” solutions of these caged compounds (c = 200-300 µM), according to the lack of effects on neuron activity or action potentials evoked by depolarization. White light photolysis by short pulses generated sufficient active substances to induce large inward currents (up to 5 nA) in Purkinje neurons
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Mariga, Shelton Tendai. "Pharmacodynamic interactions of quinolines with other antimalarial compounds in vitro /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-279-9/.
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Jacquelin, Jean-Marie. "Fonctionnalisation par métallation d'amino et d'hydroxy quinoléines : applications à la synthèse de furo quinoléines." Rouen, 1987. http://www.theses.fr/1987ROUES033.
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L'amino-2 quinoléine est fonctionnalisée par métallation en position 3. Les amino-3 et -4 quinoléines ont également été métallées respectivement sur les sommets 2 et 8 mais n'ont pu être fonctionnalisées par des électrophiles carbonés. Les hydroxy-2, -3 et -4 quinoléines masquées sous forme de carbamates sont lithiés régiosélectivement sur les carbones 3, 4 et 3 respectivement. Les dérivés ortho substitués préparés par réaction d'aldéhydes sur les intermédiaires lithiés sont utilisés pour la synthèse de furo-quinoléines
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Curry, Richard James. "Luminescence characterisation of aluminium and erbium tris (8-hydroxyquinoline)." Thesis, Queen Mary, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312173.
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Crouch, David James. "Synthesis and molecular properties of zwitterionic adducts of TCNQ and other related compounds." Thesis, Sheffield Hallam University, 1999. http://shura.shu.ac.uk/3134/.
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This thesis is concerned with the synthesis and characterisation of novel TCNQ (7,7,8,8-tetracyanoquinodimethane), TMTCNQ (2,3,5,6-tetramethyl-7,7,8,8-tetracyanoquinodimethane) and TCNQF4 (2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane) based zwitterionic D-1t-A materials (where D and A are electron donors and acceptors respectively) of which the methylated Z-~-(N-methyl-4-quinolinium)-a-cyano-4( 2,3,5,6-tetrafluoro)styryldicyanomethanide [CH3(4)Q3CNQF4] is a typical example. Synthetic modification of the donor moiety was also undertaken, resulting in a diverse range of pyridinium, quinolinium and benzothiazolium-based materials, which may have use in nonlinear optical research. For the quinolinium system an extensive range of both 2- and 4-substituted analogues have been prepared and their properties compared and contrasted. The solvatochromic behaviour of these zwitterions was investigated in detail by dissolution in a range of organic solvents and measurement of their longest wavelength charge-transfer absorption bands using UV/Visible spectroscopy, which revealed that the substituents have a marked effect upon their solvatochromic properties. Most of the adducts studied display highly negative solvatochromism as the solvent polarity increases, in which their absorption maxima are linearly related with the normalised ENT values for the Reichardt dye. However the fluorinated quinolinium and pyridinium derivatives exhibit an unusual aggregation-induced reverse solvatochromism effect. The negative halochromic behaviour of selected zwitterions has also been investigated, with a hypsochromic shift of the longest wavelength CT absorption band being observed upon addition of electrolytes. Increased polarisation within the fluorinated R(4)Q3CNQF4 and R(2)Q3CNQF4 adducts has been indicated by solution state dipole moment measurements indicating greater nonlinear optical potential. However this increased polarisation has also been shown to be a major cause of the limited stability of these materials to photo-oxidation. The behaviour of the R(4)Q3CNQF4 and R(2)Q3CNQF4 zwitterions on the subphase and their resultant Langmuir-Blodgett film forming ability was also studied. However unlike the TCNQ-based materials the fluorinated adducts have been shown to be poor LB film forming materials.
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Szamosvári, Dávid [Verfasser]. "Bacterial 2-Alkyl-4-Quinolones : Privileged Structures for the Synthesis of Bioactive Compounds / Dávid Szamosvári." Konstanz : KOPS Universität Konstanz, 2020. http://d-nb.info/1205665358/34.
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Skjonnemand, Karl. "The optical and structural characterisation of ultra-thin films." Thesis, Cranfield University, 2000. http://dspace.lib.cranfield.ac.uk/handle/1826/10739.
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Chloride, bromide, pyridinium and quinolinium homologues of 4-(N- hexadecylpyridinium-4-ylmethylidene-amino)-2,6-dichlorophenolate have been investigated in solution, Langmuir and Langmuir-Blodgett films. Techniques including spectroscopy, surface potential measurement, quartz crystal microbalance, surface plasmon resonance, atomic force microscopy, reectometry and X-ray diffraction have been used to characterise these molecular systems. In solution, solvatochroism was observed and Benisi-Hildebrand analysis revealed dimeric aggregation. Langmuir monolayers were compressed at the air/water interface and chromophore rotation was observed by surface potential measurement. Langmuir- Blodgett monolayers showed lm-thickness dependence on the deposition-pressure. Monolayer thicknesses between 6-24Ä were measured using SPR and molecular areas between 40-l25Ä2 were measured using a quartz crystal microbalance. Both the molecular/s/area)and monolayer thicknesses were deposition-pressure dependent. The high tilt phases were visually distinguishable from the low tilt phases using atomic force microscopy, The compounds showed phase behaviour that was predominantly alike for the bromide and chloride homologues but different for the pyridinium and quinolinum homologues. Multilayer Y-type films of the merocyanine dyes were analysed using reectometry and deposition-pressure dependent thicknesses were found. Alternate layer structures of NLO-active hemicyanine amphiphiles were used to achieve homogeneous. orientation ordering using active and inactive spacer layers. Ordering was achieved but the optical efficiency was reduced by high proportions of inactive material and interlayer dipole formation. Double chained hemicyanine molecules were used to form Z-type structures and subsequent layers were found to significantly interdigitate. Different chain lengths were found to interdigitate by the length of the shortest chain. Gas detection experiments were undertaken on the quinolinium, dichloro merocyanine using three optical geometries. The absorption method showed slow switching and poor sensitivity. The Kretschmann SPR geometry showed high sensitivity and rapid switching. The grating SPR geometry showed rapid switching but was less sensitive than the ATR method. Protonation of the monolayers was investigated using hydrochloric acid gas, acetic acid vapour and stearic acid immobilised within the lm.
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Folmar, Michele L. "Synthesis and Characterization of a New Ruthenium(II) Polypyridyl Compound with a Quinolate-Type Ligand." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1469047981.
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Machado, Rafael Carvalhaes. "Síntese, caracterização e avaliações biológicas de 4-piridinil, 7-cloro-4-quinolinil e 9-acridinil, semicarbazidas e tiossemicarbazidas." Universidade Federal de Juiz de Fora, 2016. https://repositorio.ufjf.br/jspui/handle/ufjf/1143.
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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A presente tese, intitulada "Síntese, caracterização e avaliações biológicas de 4-piridinil, 7-cloro-4-quinolinil e 9-acridinil, semicarbazidas e tiossemicarbazidas" descreve a preparação, caracterização e avaliação do potencial biológico de compostos sintéticos híbridos contendo uma porção heterocíclica (núcleo piridínico, quinolínico ou acridínico) associada a uma subunidade tiossemicarbazida ou semicarbazida N-4 substituída. Os compostos almejados foram preparados por duas rotas sintéticas distintas: 1) via reação de substituição nucleofílica aromática entre os derivados halo-heterocíclicos (4-cloropiridina, 4,7-dicloroquinolina e 9-cloroacridina) e as tiossemicarbazidas e semicarbazidas N-4 substituídas e 2) via reação de adição dos derivados heterocíclicos de hidrazina (4-hidrazinopiridina, 7-cloro-4-hidrazinoquinolina e 9-hidrazinoacridina) aos isotiocianatos e isocianatos. As estruturas químicas dos produtos obtidos, bem como as dos intermediários sintéticos, foram caracterizadas por faixa de fusão, espectroscopia no infravermelho, de ressonância magnética nuclear de hidrogênio e de carbono-13 e por espectrometria de massas. Os compostos sintetizados foram avaliados como potenciais agentes antibacterianos (S. aureus, E. coli, P. aeruginosa e S. typhimurium), antituberculares (M. tuberculosis) e antitumorais. Enquanto alguns dos compostos avaliados apresentaram atividade antibacteriana promissora, nenhum dos compostos sintéticos pode ser considerado candidato a agente anti-TB. Em relação a atividade antitumoral, a maioria dos compostos avaliados exibiu elevada citotoxicidade.
The present thesis, entitled “Synthesis, characterization and biological evaluation of 4-pyridinyl, 7-chloro-4-quinolinyl, 9-acridinyl, semicarbazides and thiossemicarbazides”, describes the preparation, characterization and evaluation of the biological potential of synthetic hybrid compounds containing a heterocyclic moiety (pyridine, quinoline or acridine ring) associated with an N-4 substituted semicarbazide or thiosemicarbazide subunit. The desired compounds were prepared by two different synthetic routes: 1) via nucleophilic aromatic substitution reaction between the halo-heterocyclic derivatives (4-chloropyridine, 4,7-dichloroquinoline and 9-chloroacridine) and N-4 substituted thiosemicarbazides and semicarbazides and 2) via addition reaction of the heterocyclic hydrazine derivatives (4-hydrazinopyridine, 7-chloro-4-hydrazinoquinoline and 9-hydrazinoacridine) to isothiocyanates and isocyanates. The chemical structures of the products obtained, as well as synthetic intermediates, were characterized by their melting points, infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies and by mass spectrometry. The compounds synthesized were evaluated as potential antibacterial (S. aureus, E. coli, P. aeruginosa e S. typhimurium), antituberculosis (M. tuberculosis) and antitumor agents. While some of the evaluated compounds showed promising antibacterial activity, none of the compounds synthesized may be considered a candidate as an anti-TB agent. With respect to antitumor activity, the majority of the evaluated compounds exhibited high cytotoxicity.
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Fournel, Jean-Louis. "Synthèse et étude de nouveaux agonistes dopaminergiques : les amino hydroxy tetrahydro quinoléines." Rouen, 1986. http://www.theses.fr/1986ROUES029.
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Synthèse d'hydroxy- ou dihydroxy amino-3 tetrahydro-1,2,3,4 quinoléines par réduction par NABH4 ou par hydrogénations sur palladium d'amino-3 quinoléines ; études de relation structure activité ; calculs MNDO et CNDO
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Zwergel, Clemens. "Synthesis and biological evaluation of various heterocyclic compounds : Aurones from Coumarins and Chromones, Quinolines and Pyrimidines as DNMTi, Coumarins as potential NF-kB inhibitors." Thesis, Université de Lorraine, 2013. http://www.theses.fr/2013LORR0276/document.
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Aujourd'hui, le cancer est devenu un problème majeur de santé publique avec 12,7 millions de nouveaux cas de cancer et 7,6 millions de décès enregistrés en 2008. Même si le nombre des personnes qui guérissent augmente, les décès sont toujours importants. Les raisons, malgré un diagnostic précoce et correct, sont l'absence de traitements efficaces et l'émergence des résistances à la thérapie anticancéreuse. C'est pourquoi les chercheurs s'intéressent aux nouvelles approches pour développer des traitements puissants et sélectifs pour vaincre le cancer. Dans notre première approche, nous avons développé une série de dérivés de composés naturels appelés aurones. Les aurones jouent un rôle important dans la pigmentation jaune lumineuse de certaines fleurs et certains fruits et montrent des nombreuses activités biologiques. Nous avons combiné le motif benzofuranone des aurones avec d'autres motifs de la coumarine et chromone inspirées par la nature. Ces nouveaux composés montrent une activité anticancéreuse prometteuse, car ils sont capables de bloquer le cycle cellulaire dans les cellules cancéreuses K562 et peuvent y induire l'apoptose. Ils sont donc un motif intéressant pour un développement ultérieur de recherches. Ensuite nous avons concentré notre attention sur un objectif épigénétique. Les méthyltransférases d'ADN sont considérées comme une cible intéressante en oncologie. L'usage d'inhibiteurs spécifiques de la méthyltransferase d'ADN (DNMTi) pourrait réactiver les gènes suppresseurs de tumeurs et induire la reprogrammation des cellules cancéreuses, conduisant à l'arrêt de leur prolifération et finalement à leur mort. Nous avons amélioré le composé connu SGI1027 par modification de la structure. Nous avons obtenu des nouveaux inhibiteurs de la méthyltransferase d'ADN non- nucléosidiques, plus puissants et plus sélectifs que le composé principal. L'activité anti-cancéreuse de nos composés quinoléiniques et pyrimidiniques est testée sur différentes lignées cellulaires de cancer indiquant leur future utilisation possible dans un traitement anti-cancéreux puissant et sélectif. Une troisième série d'analogues de curcuminoïdes à base de coumarine a été préparée et testée pour sa capacité potentielle à moduler la voie TNF-alpha induit par NF-kB dans les cellules cancéreuses K562. Cependant, nous n'avons pas été capable de montrer l'implication de la voie ciblée jusqu'à maintenant. Des études complémentaires et plus approfondies doivent être menées afin d'estimer les propriétés biologiques de ces composés dans la participation éventuelle à différentes voiesToday, cancer is becoming a major public health problem with 12.7 million new cancer cases and 7.6 million cancer deaths registered in 2008. Although the number of people cured of cancer is increasing, people still die because of cancer. The reasons, besides an early and correct diagnosis, are the lack of effective treatments and the emergence of drug-resistant cancers. Therefore, researchers are interested in new approaches to develop potent and selective therapies to fight cancer. To start with, we developed a series of natural compound derivatives related to aurones. Aurones play an important role in the bright yellow pigmentation of some flowers and fruits exhibiting a strong and broad variety of biological activities. We combined the benzofuranone motif of the aurone with other coumarin and chromone motifs inspired by nature. These new compounds displayed spromising anticancer activity because they are able to block the cell cycle in K562 cancer cells and are able to induce apoptosis being an interesting scaffold for further development. Secondly, we focused on an epigenetic target. DNA methyltransferases are considered as an interesting target in Oncology. The use of specific inhibitors of DNMT (DNMTi) might reactivate tumor suppressor genes and induce the reprogramming of cancer cells, leading to their proliferation arrest and ultimately to their death. We improved the known compound SGI1027 through structure modification leading to novel non-nucleoside DNMT inhibitors, more potent and more selective than the lead compound. The anticancer activity of our quinoline and pyrimidine based compounds - tested in different cancer cell lines - suggests their use as possible potent and selective future cancer therapy. A third series of coumarin-based curcuminoid analogues were prepared and tested for their potential ability to modulate the TNF-alpha induced NF-kB pathway in K562 cancer cells. However we were not able to demonstrate the involvement of the targeted pathway so far. Complementary and deeper investigations need to be conducted in order to elicit deeper biological properties of these compounds with the possible involvement of different pathways
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Cabarrocas, Duran Gemma. "Aproximacions sintètiques per a la preparació estereoselectiva de noves quinolil i pirazolilglicines i per a la preparació en fase sòlida de llibreries de benzotiazoles, 1,2,4-triazines i benzimidazoles." Doctoral thesis, Universitat de Girona, 1999. http://hdl.handle.net/10803/8057.
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El treball experimental que ha permès redactar la present Tesi Doctoral ha estat dividit en dues parts. A la primera part es presenten els resultats referents a la síntesi estereocontrolada de noves heteroarilglicines (quinolil i pirazolilglicines) a partir de cetones acetilèniques, substrats quirals que permeten accedir a l'esquelet de diferents heterocicles (quinolines i pirazoles), la posterior obtenció dels corresponents quinolil i pirazolil--aminoalcohols i les diferents metodologies d'oxidació per tal d'accedir a les corresponents quinolil i priazolilglicines objectiu. A la segona part d'aquesta memòria s'ha estudiat, en dissolució, l'habilitat del grup alquilsulfona com a grup sortint eficaç en reaccions d'ipso-substitució nucleofilica. El desenvolupament d'aquesta reacció ha servit de punt de partida per a la creació de llibreries d'heterocicles amb alta diversitat molecular i potencial interès biològic sobre fase sòlida.These work have been divided in two sections. In the first section, a new and efficient methodology towards the stereocontrolled synthesis of novel -acetylenic ketones containing a masked -amino acid functionality in enantiomerically pure form has been developed. This new chiral building block is the starting material for the synthesis of enantiomerically pure quinolyl and pyrazolylglycines, important structures with potential biological activity and very useful for the synthesis of peptidomimetics. The methods begins from the Garner's aldehyde and takes place through an alkyne derivative via a carbonyl-alkyne homologation reaction. Condensation of the lithium acetylide at low temperatures with different aldehydes yielded the corresponding propargyllic alcohol derivatives in good yields, which under mild oxidative conditions gave the corresponding acetylenic ketones algmost quantitatively.In the second part of this work, the ability of alkylsulfonyl groups as efficient leaving groups in heteroaromatic mucleophilic ipso-substitution reactions has been studied. The rational behind this study has been the possibility of transferring the developed methodology to the solid support and thus to synthesize in a parallel fashion a small library of molecularly diverse heterocycles with potential biological interest. An in solution optimised methodology has been successfully transferred to the solid support and a small library of molecularly diverse benzothiazoles (-excedent heterocylces) was prepared in a parallel fashion in good overall yields and purities of the final products.
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Charavin, Marine. "Synthèse d'agonistes non-peptidiques du récepteur à la prokinéticine PKR1." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF047/document.
Full textAbstract:
Les récepteurs couplés aux protéines G représentent la plus grande famille de récepteurs membranaires. Parmi eux, nous avons choisi d’étudier deux récepteurs apparentés : les récepteurs de la prokinéticine 1 et 2. Ces deux récepteurs ont pour ligands des hormones de nature peptidique, divisées en deux sous-groupes : les prokinéticines 1 et 2. Ces deux prokinéticines sont impliquées dans plusieurs processus physiologiques en se liant à leurs récepteurs PKR1 et PKR2. Il a été récemment montré que la prokinéticine 2 pouvait stimuler la prolifération et la différenciation des cellules souches progénitrices cardiaques, via les récepteurs PKR1 et PKR2. Il a également été reporté que l’activation de PKR1 protège les cardiomyocytes et les cellules progénitrices cardiaques de l’apoptose. Afin d’étudier ces effets nous avons synthétisé des agonistes non-peptidiques du récepteur PKR1. Nous avons donc poursuivi les études de pharmacomodulation d’une première famille de composés et développé une seconde famille d’agonistes potentiels originaux, déterminée par des études de modélisation moléculaire. Une sonde fluorescente a été synthétisée afin d’évaluer la liaison de nouveaux composés. Au cours de ces travaux nous avons découvert une nouvelle réaction multi-composante permettant la synthèse d’un composé dihydropyrrole polyfonctionnel. Nous nous sommes alors intéressés à son mécanisme et à sa limitation chimique dans le but de former de nouveaux hétérocycles fonctionnalisésThe G protein-coupled receptors represent the largest familly of membrane receptors. Among them,we choose to study two related receptors: prokineticin receptors 1 and 2. These two receptors have peptidic hormone ligands, divided in two sub-groups: prokineticins 1 and 2. Both prokineticins are involved in many physiological processes by binding to their receptors PKR1 and PKR2. It has recently been shown that prokineticin 2 could stimulate proliferation and differentiation of cardiac progenitor cells. It was also reported that activation of PKR1 protects cardiomyocytes and cardiac progenitor cells from apoptosis. To investigate these effects we synthesized non-peptidic receptor PKR1. We continued pharmacodulation studies of a first familly of compounds and developped a second familly of original potential agonists, determined by molecular modeling studies. A fluorescent probe was synthesized to access the binding of novel compounds. During this work we discovered a new multi-component reaction for the synthesis of a polyfunctional dihydrpyrrol compound. We then interested in the mechanism and its chemical limitation in order to form new functionalized heterocycles
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Brunet, Sylvette. "Mode d'action des catalyseurs d'hydrodesazotation des coupes petrolieres : decomposition de quinoleines et d'anilines sur catalyseurs a base de sulfures de nickel et de molybdene." Poitiers, 1987. http://www.theses.fr/1987POIT2287.
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Benaissa, Tahar. "Synthèse de ligands contenant un atome de fluor et pouvant donner des complexes à applications médicales : étude de la complexation de la 5-fluoro-8-hydroxyquinoline avec des cations métalliques, par RMN du fluor." Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10100.
Full textAbstract:
Ce travail se place a la convergence de deux grands themes etudies au laboratoire: le marquage de molecules par un atome de fluor et l'etude de la complexation de cations metalliques par des ligands. La premiere partie concerne la preparation de deux series de ligands contenant du fluor: des biphenols et des composes contenant des groupements 2-fluoropyridines. Les biphenols substitues par deux ou quatre atomes de fluor (en position 4,4' ; 5,5' ; 4,4 ;,5,5') ont ete obtenus a partir de bromophenols par une reaction de type ullman. Leurs derives sulfones ont egalement ete prepares pour augmenter la solubilite dans l'eau. Les ligands de la seconde serie, tel la n,n,n',n' tetrakis(6-fluoro-2-pyridylmethyl)ethylenediamine, ont ete obtenus par alkylation de differentes amines avec la 2-fluoro-6-bromomethylpyridine, dans des conditions de transfert de phase. Ces ligands ont ete caracterises par rmn du #1h, #1#9f et #1#3c et des resultats interessants, concernant les constantes de couplage, ont ete observes. Ces deux familles de ligands ont ete prepares afin de permettre, par la suite, une etude de leur complexation par rmn du #1#9f, analogue a celle entreprise dans la partie suivante. La seconde partie concerne l'etude de la complexation de la 5-fluoro-8-hydroxyquinoline (fox) avec des cations metalliques (le gallium et le fer) par rmn du #1#9f et par spectroscopie uv-visible. Concernant l'etude de la complexation de ga par la fox utilisant la rmn du fluor nous avons constate que les trois complexes gafox, gafox#2 et gafox#3 ont des deplacements chimiques du fluor differents, obtenu les diagrammes de repartition des especes en fonction du ph pour differents rapports molaires c#m/c#f#o#x (c#m et c#f#o#x sont les concentrations en metal et ligand) et calcule les trois constantes de formation des complexes gafox, gafox#2 et gafox#3. Le complexe gafox#3 a egalement ete etudie seul en solvant organique (dmf-d7). Nous avons mis en evidence que dans ce complexe, qui existe presque uniquement sous la forme de l'isomere mer, les trois ligands subissent une interconversion intramoleculaire rapide
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Mongin, Florence. "Régiosélectivité des réactions de bromation, d'échange halogène-métal et de couplage croisé sur des dérivés de la 8-hydroxyquinoléine. Application à la synthèse de pyridocarbazoles." Rouen, 1994. http://www.theses.fr/1994ROUES063.
Full textAbstract:
Les 8-hydroxy et 8-méthoxyquinoléines étudiées peuvent subir une réaction de bromation ; ainsi sont obtenues des quinoléines diversement substituées par des atomes de brome en position 3, 5 et 7. A partir des 5,7-dibromoquinoléines substituées en position 8, un échange brome-lithium sélectif a été réalisé ; la nature du substituant en position 8 modifie l'orientation de cette réaction. La réaction de couplage croisé, appliquée à diverses bromo-8-méthoxyquinoléines, permet de greffer différents groupements. Dans le cas de dibromoquinoléines, une bonne régiosélectivité a été observée. Enfin, de nombreux pyridocarbazoles ont été synthétisés, la réaction de couplage croisé étant utilisée pour créer la jonction entre les cycles quinoléinique et benzénique
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Jallal, Houda. "A Src-Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth and metastasis in vitro and in vivo /." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112641.
Full textAbstract:
The central role of Src in the development of several malignancies including breast cancer and the accumulating evidence of its interaction with receptor tyrosine kinases (RTK), integrins and steroid receptors have identified it as an attractive therapeutic target. In the current study we have evaluated the effect of a Src/Abl kinase inhibitor SKI-606, on breast cancer growth, migration, invasion and metastasis. Treatment of human breast cancer cells MDA-MB-231 with SKI-606 caused a marked inhibition of cell proliferation, invasion and migration by inhibiting MAPK and Akt phosphorylation. For in vivo studies MDA-MB-231 cells transfected with the plasmid encoding green fluorescent protein (GFP) [MDA-MB-231-GFP] were inoculated into mammary fat pad of female BALB/c nu/nu mice. Once tumor volume reached 30-50 mm3, animals were randomized and treated with vehicle alone or 150 mg/kg of SKI-606 by daily oral gavage. Experimental animals receiving SKI-606 developed tumors of significantly smaller volume (45-54%) as compared to control animals receiving vehicle alone. Analysis of lungs, liver and spleen of these animals showed a significant decrease in GFP positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated. Western blot analysis and immunohistochemical analysis of primary tumors showed that these effects were due to the ability of SKI-606 to block tumor cell proliferation, angiogenesis, growth factors expression and inhibition of Src mediated signalling pathways in vivo. Together the results from these studies provide compelling evidence for the use of Src inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.
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Dobrachinski, Fernando. "ASSOCIAÇÃO DO DISSELENETO DE DIFENILA E MODULADORES DO SISTEMA GLUTAMATÉRGICO FRENTE AO DANO OXIDATIVO CAUSADO POR ÁCIDO QUINOLÍNICO." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/11214.
Full textAbstract:
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorExcessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been hypothesized as key mechanisms contributing to quinolinic acid (QA)- induced toxicity. Thus, here we investigate if the use of diphenyl diselenide (PhSe)2, guanosine (GUO) and MK-801, alone or in combination, could protect rat brain slices from QA-induced toxicity. QA (1 mM) increased ROS formation, thiobarbituric acid reactive substances (TBARS) and decreased cell viability after 2 h of exposure. (PhSe)2 (1 μM) protected against this ROS formation in the cortex and the striatum and also prevented decreases in cell viability induced by QA. (PhSe)2 (5 μM) prevented ROS formation in the hippocampus. GUO (10 and 100 μM) blocked the increase in ROS formation caused by QA and MK-801 (20 and 100 μM) abolished the pro-oxidant effect of QA. When the non effective concentrations were used in combination produced a decrease in ROS formation, mainly (PhSe)2 + GUO and (PhSe)2 + GUO + MK-801. These results demonstrate that this combination could be effective to avoid toxic effects caused by high concentrations of QA. Furthermore, the data obtained in the ROS formation and cellular viability assays suggest different pathways in amelioration of QA toxicity present in the neurodegenerative process.
A formação excessiva de espécies reativas de oxigênio (ROS) e alterações na captação de glutamato têm sido associadas como mecanismos chave que contribuem para toxicidade induzida pelo ácido quinolínico (AQ). Assim, nós investigamos se a utilização do disseleneto de difenila (PhSe)2, guanosina (GUO) e MK-801, isoladamente ou em combinação, podem proteger as fatias de regiões cerebrais de ratos da toxicidade induzida por AQ. AQ (1 mM) aumentou a formação de ROS, substâncias reativas ao ácido tiobarbitúrico (TBARS) e diminuiu a viabilidade celular após 2h de exposição. (PhSe)2 (1 μM) protegeu contra esta formação de ROS no córtex e no estriado e além disso preveniu a diminuição da viabilidade celular induzida pelo AQ. (PhSe)2 (5 μM) preveniu a formação de ROS no hipocampo. GUO (10 e 100 μM) bloqueou o aumento na formação de ROS causada pelo AQ e MK-801 (20 e 100 μM) aboliu o efeito pró-oxidante do AQ. Quando as concentrações não-efetivas foram usadas em combinação produziram uma diminuição na formação de ROS, principalmente (PhSe)2 + GUO e (PhSe)2 + GUO + MK-801. Estes resultados demonstram que esta combinação pode ser eficaz para evitar os efeitos tóxicos provocados por concentrações elevadas do AQ. Além disso, os dados obtidos nos ensaios de formação de ROS e viabilidade celular sugerem diferentes vias de atuação na melhora da toxicidade induzida pelo AQ presente no processo neurodegenerativo.
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Demonchaux, Patrice. "Recherche d'agents radioprotecteurs : synthèse et mécanisme d'action de composés de type intercalant-aminothiol." Grenoble 1, 1988. http://www.theses.fr/1988GRE10016.
Full textAbstract:
Les intercalants utilises sont des amino-9 chloro-6 methoxy-2 acridines des amino-4 chloro-7 quinoleines et des amino-4 chloro-7 methyl-1 quinoleiniums sur lesquels ont ete introduites des chaines analogues a celles de la cysteamine et du wr 2727; etude de l'affinite de ces composes avec l'adn
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RUHLAND-FRITSCH, BEATRICE. "Synthese et etude pharmacologique de derives benzeniques d'analogues du gaba." Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR13056.
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Ferroud, Clotilde. "Étude de la réaction de Diels-Adler intra et intermoléculaire sous haute pression : application à la synthèse stéréosélective d'alcaloïdes de l'indole du groupe des yohimbanes." Paris 6, 1986. http://www.theses.fr/1986PA066023.
Full textAbstract:
Le schéma de synthèse repose sur une unité bicyclique, précurseur direct des unités (d,e) du squelette pentacyclique. Cet intermédiaire est basé sur une réaction de Diels-Alder sous haute pression, utilisant la cycloaddition de diènes de structure donneur-accepteur 1,4 avec une lactone insaturée comme diénophile. La synthèse du système pentacyclique est exposée à partir de cet intermédiaire clé.
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Boukhalfa, Hakim. "Complexation du fer par des ligands tripodes à base de sous-unités 8-hydroxyquinoléine et 2,2'dihydroxybiphényle : aspects thermodynamiques et cinétiques." Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10250.
Full textAbstract:
Ce travail concerne des etudes thermodynamiques et cinetiques de la complexation du fer(iii) par des ligands possedant des sites de coordination de type 8-hydroxyquinoleine et 2,2'-dihydroxybiphenyle. La premiere partie a concerne l'etude des complexes ferriques des ligands 8-hq (oxine), 5-so#3#, 8-hq (sulfoxine) et 5-f-8-hq (fluorooxine). Les resultats mettent en evidence l'influence des proprietes electroniques des sites de coordination sur la stabilite des complexes. Quand la coordination du fer par le ligand n'est pas complete, des hydroxo complexes sont formes. Les etudes cinetiques de formation et d'hydrolyse acide des complexes permettent une approche du mecanisme de formation et d'hydrolyse du complexe. Le mecanisme est exprime en terme d'une succession d'etapes de formation et de coupure des liaisons n-fe et o-fe. La seconde partie a ete consacree a l'etude thermodynamique et cinetique de la complexation de l'ion fe#3#+ avec des ligands de structure tripode o-trensox et n-trensox a sous-unites 8-hydroxyquinoleine. La caracterisation des ligands ainsi que des a permis de determiner les constantes d'equilibre et d'obtenir egalement des informations structurales a l'aide des methodes spectrophotometriques uv-vis, ir et potentiometriques. La cinetique de formation du complexe fe(o-trensox) en milieu acide ainsi que sa cinetique d'hydrolyse acide ont ete etudiees afin de mettre en evidence les mecanismes de complexation du fer par le ligand et de sa sortie de la cage de coordination formee par le ligand. Les resultats des etudes cinetiques d'echanges de l'ion fe#3#+ entre la transferrine, l'edta et o-trensox permettent de proposer un mecanisme pour l'echange du fer entre la transferrine et le ligand o-trensox. La troisieme partie concerne l'etude thermodynamique et cinetique de la complexation du fer par un ligand biphenol et son homologue tripode. Cette etude de physico-chimie en solution permet de mieux comprendre les interactions cations metalliques-ligands dans les perspectives de conception de molecules actives dans le domaine de la sante et de l'agrochimie
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Ferreira, João Paulo de Sousa. "Novel heterocyclic quinoline/quinolone-based compounds as acetylcholinesterase inhibitors and antioxidant agents." Master's thesis, 2019. http://hdl.handle.net/10773/30140.
Full textAbstract:
Alzheimer’s disease represents about 60-80% of all cases of dementia, mainly
affecting people over 65 years. This pathology is caracterizated at the molecular
level by the presence of senile plaques (Aβ amyloid peptides aggregates) and
neurofibrillary tangles (NFTs). In addition, several experimental studies have
revealed that acetylcholinesterase (AChE) enzyme plays a crucial role in the
development of Alzheimer’s disease, leading to the formation of NFTs and senile
plaques. Oxidative stress is a cause and consequence of this pathology,
activating signalling pathways that promote Aβ peptides aggregation, which in
turn are detected by microglia cells, leading to the formation of free radicals,
including NO•
, which, in turn, contributes to the marked neuroinflammation in this
pathology. In this context, the development of AChE inhibitors and antioxidants,
namely as radical scavengers, continue to deserve attention from researchers.
The aim of the present work was the synthesis, structural characterization
(mono-(
1H and 13C) and two-dimensional (HMBC and HSQC) nuclear magnetic
resonance (NMR) spectroscopy, mass spectrometry, high resolution mass
spectrometry and x-ray) of (aryl)(furo [3,2-c] quinolin-2-yl)methanones, 3-(3-aryl4,5-dihydro-1H-pyrazol-5-yl)-4-chloroquinolines and, as exploratory approach,
(E)-3-(2-hydroxyphenyl)-5-(4-methoxystyryl)isoxazole for the evaluation of AChE
inhibitory activity and antiradical activity.
The anticholinergic and antiradical activities of the synthesized compounds were
evaluated using Ellman's method and radical scavenging assays for (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•
) and NO•
, respectively.
Whenever possible, the obtained values were expressed as a function of the
concentration of compound which promoted 50% of inhibition of enzymatic
activity or promoted 50% of radicals scavenging (IC50), respectively, to establish
some biological structural-activity relationships.
(Aryl)(furo[3,2-c]quinolin-2-yl)methanones were not effective as antiradical
agents, however two derivatives exhibited AChE inhibitory activities (IC50 < 100
µM). 3-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-4-chloroquinolines and (E)-3-(2-
hydroxyphenyl)-5-(4-methoxystyryl)isoxazole were good ABTS+• scavenger
agents but were not very effective in NO• scavenging, presenting for most
derivatives IC50 > 700 µM. 3-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-4-
chloroquinolines showed promising AChE inhibitory activities with most
derivatives having IC50 < 100 µM, while (E)-3-(2-hydroxyphenyl)-5-(4-
methoxystyryl)isoxazole was not very effective against this enzyme.
These results showed that some of the synthesized compounds have potential
as AChE inhibitors and antioxidant agents.A doença de Alzheimer representa cerca de 60 a 80% dos casos de demência afetando principalmente indivíduos com idades superiores a 65 anos. Esta patologia é caracterizada, a nível molecular, pela presença de placas senis (agregados de péptidos de Aβ amilóide) e agregados neurofibrilares (NFTs). Além disso, diversos estudos experimentais têm revelado que a enzima acetilcolinesterase (AChE) participa no desenvolvimento desta patologia, culminando na formação de NFTs e placas senis. O stress oxidativo é uma causa e consequência desta patologia, ativando vias de sinalização que promovem a agregação dos péptidos Aβ, que por sua vez, são detetados pelas células da microglia, levando à produção de radicais livres incluindo óxido nítrico (NO• ) que, por sua vez, contribuem para a neuroinflamação marcada nesta patologia. Neste contexto, o desenvolvimento de inibidores da AChE e de antioxidantes, nomeadamente como agentes captadores desses radicais, continuam a merecer atenção por parte dos investigadores. O presente trabalho teve por objetivo a síntese, caracterização estrutural (espectroscopia de ressonância magnética nuclear (RMN) mono- ( 1H e 13C) e bidimensionais (HMBC e HSQC), espetrometria de massa, espetrometria de massa de alta resolução e raio-x) de (aril)(furo[3,2-c]quinolin-2-il)metanonas, 3- (3-aril-4,5-di-hidro-1H-pirazol-5-il)-4-cloroquinolinas e ,a título exploratório, de (E)-3-(2-hidroxifenil)-5-(4-metoxiestiril)isoxazol para avaliação da atividade inibitória da AChE e antiradicalar. As atividades anticolinérgicas e antiradicalar dos compostos sintetizados foram avaliadas recorrendo aos métodos de Ellman e de avaliação da capacidade de captação dos radicais (ácido 2,2'-azino-bis(3-etilbenzotiazolina-6-sulfónico) (ABTS+•) e NO• , respetivamente. Sempre que possível, os valores obtidos foram expressos em função da concentração de composto que promoveu a inibição de 50% da atividade enzimática ou que promoveu 50% de captação dos radicais (IC50), respetivamente, para serem estabelecidas algumas relações estruturaatividade biológica. As (aril)(furo[3,2-c]quinolin-2-il)metanonas não se mostraram efectivas como agentes antiradicalares, no entanto dois derivados exibiram atividades inbitórias da AChE (IC50 < 100 µM). As 3-(3-aril-4,5-di-hidro-1H-pirazol-5-il)-4- cloroquinolinas e o (E)-3-(2-hidroxifenil)-5-(4-metoxiestiril)isoxazol foram bons agentes captadores do ABTS+• no entanto não foram muito efetivos na captação do NO• , apresentando para a maior parte dos derivados IC50 > 700 µM. As 3-(3- aril-4,5-di-hidro-1H-pirazol-5-il)-4-cloroquinolinas apresentaram atividades inibitórias de AChE promissoras com maior parte dos derivados apresentando IC50 < 100 µM, enquanto o (E)-3-(2-hidroxifenil)-5-(4-metóxiestiril)isoxazol não foi muito efetivo contra esta enzima. Os resultados evidenciaram que alguns compostos sintetizados apresentaram potencial como inibidores da AChE e como agentes antioxidantes.
Mestrado em Bioquímica
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Hlungwani, Isaac. "Design, synthesis and biological evaluation of novel tetrasubstituted quinoline-3-carboxamides derivatives." Diss., 2020. http://hdl.handle.net/11602/1558.
Full textAbstract:
MSc (Chemistry)Department of Chemistry
Quinolines are well known naturally occurring heterocyclic compounds with nitrogen as a heteroatom. Quinolines are also one of the major classes of naturally occurring compounds and the interest in their chemistry is due to the wide range of their biological activities. The objective of the project was the synthesis of novel tetra-substituted quinoline-3carboxamides and subsequent transformation to other novel derivatives and evaluation of their biological activities against malaria and cytotoxicity. In achieving the objective, 2-chloroquinoline-3-carbaldehyde analogues 54A-G were synthesised from the reaction of acetanilides 53A-G and acetic acid. Knoevenagal reaction of 2chloroquinoline-3-carbaldehydes 54A-G with thiazolidinedi-2,4-one 62 provided 2chloroquinoline-3-methylene thiazolidinedi-2,4-one 55A-G which then underwent nucleophilic substitution reaction with sodium azide and afforded (Z)-5-((tetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56A-F. (Z)-ethyl-2-(2-5-((7bromotetrazolo [1,5a] quinolin-4-yl) methylene-2,4-dioxothiazolidin-3-yl) acetamido) acetate 57 was synthesised from the reaction of (Z)-5-((7-bromotetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56D and ethyl-2-(2-chloroacetamido) acetate 65. The structures of the compounds were characterised by 1D NMR (1H, 13C, and DEPT 135), IR spectroscopy, elemental analysis and high-resolution mass spectroscopy. Novel selected synthesised quinoline compounds were evaluated of in vitro for two biological assays; namely anti-malarial activity and cytotoxicity. The anti-malaria activities of the novel quinoline compounds against 3D7 strain of the malaria parasite Plasmodium falciparum displayed that 2,6-dichloroquinoline-3-methylene thiazolidinedi-2,4-one 55C, (Z)-5-((7-fluorotetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56B and (Z)-5((7-ethoxytetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56F are potential malaria drugs since they reduced the percentage parasite viability to 25.80, 12.40 and 20.40 respectively. These results were further substantiated by their IC50 values 0.40, 0.04 and 0.50 µg/mL. Compound 56B displayed the highest cytotoxicity activity against human cervix adenocarcinoma cells displaying percentage viability of 14.22 %. Compounds 56F and 56C displayed moderate cytotoxicity activity at 56.60 and 59.81 % viability.
NRF
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tsai, Pei-Hsun, and 蔡珮熏. "Cytotoxic Mechanism of Quinoline-Derived Compounds in Human Prostate Cancer." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/61873093426763527250.
Full textAbstract:
碩士高雄醫學大學
醫學系生物化學科碩士班
103
Although hormone-sensitive prostate cancer could be treated by hormone therapy, it will eventually progress to castration-resistant prostate cancer (CRPC).The chemotherapeutic agent, docetaxel has been used as a prostate chemotherapy drug for years. Significant outcome has been observed in CRPC patients, but most of them will ultimately develop docetaxel resistance. Hence, to understand the mechanism behind development of drug resistance has become imperative and important. Previous research found that the docetaxel-resistant cell line PC/DX 25 expresses a higher EGFR level than PC3. This study aimed to screen new compounds that inhibit EGFR downstream as a treatment for docetaxel-resistant prostate cancer. First, the IC50 of quinoline-derived compounds were tested using MTT assay. BV001, BV005 and BV006 were found to have lower IC50. The cytotoxicity of BV001 was 2.3 folds higher in PC3 cells than in PC/DX 25 cells. Moreover, EGFR overexpression cell line, A431, had higher sensitivity to BV001 than other compounds. Real-time PCR and western blot analyses found that mRNA and protein levels of EGFR were reduced in both PC3 and PC/DX 25 cells after BV001 treatment. Examining downstream molecules revealed that BV001 inhibited the expression of STAT3 as well as the expression and activity of AKT in two cell lines. However, in PC3 cells, BV001 induced ERK activity. Furthermore, by western blot, after BV001 treatment, the expression of apoptosis-related molecules was up-regulated and the expression of anti-apoptotic molecules was down-regulated in both PC3 and PC/DX 25 cell lines. In addition, ABCB1 was reduced by BV001 treatment in these two cell lines. Flow cytometry found that reactive oxygen species (ROS) were produced in cells after BV001 treatment. After the activity of ERK was inhibited, PC3 increased its sensitivity to BV001. According to the above results, BV001 led cells to apoptosis via affecting the EGFR pathway.
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Chang, Jia-Hen, and 張嘉恆. "Supramolecular Au(I) Compounds Containing Trithiocyanuric acid or Quinoline-8-thiolate." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/6qkcmp.
Full textAbstract:
碩士國立中正大學
化學暨生物化學研究所
105
In the literature, most of the closed-shell d10 gold(I) complexes containing phosphine or thiolate ligands, show intriguing structural and spectroscopic properties. In this thesis, we used AuClPMe3 and AuClPEt3 (PMe3 = trimethylphosphine；PEt3 = triethylphosphine) to react with thiolate ligands H3N3S3 (Trithiocyanuric acid) and H8-QNS (Quinoline-8-thiolate) to construct dinuclear, trinuclear, and hexanuclear gold(I) compounds. Crystal structures of compound 1-4 are determined by single-crystal X-ray crystallography, [(N3S3)Au(AuPMe3)2]2‧2CH2Cl2 (1), [(N3S3)Au(AuPEt3)2]2‧C2H5OH (2), [(8-QNS)2Au(AuPMe3)2]2‧2ClO4‧2CH2Cl2 (3) and [(8-QNS)2(AuPEt3)4(ClO4)2] (4). Complexes 1 and 2 are hexanuclear structure, where four Au(I) centers are arranged in the form of a parallelogram with Au(I)…Au(I) distances of 2.950(1), 2.965(1) Å and 2.990(1), 2.958(1) Å, respectively. Complex 3 is a trinuclear structure, where the central Au(I) center is bonded with two 8-QNS, and two AuPMe3 are bonded with two different 8-QNS ligands, which are further aggregated to form a hexanuclear supermolecule through intermolecular Au(I)…Au(I) contacts of 3.192(1), 3.108(1) and 3.218(1) Å. Complex 4 is a dinuclear structure, where two AuPEt3 are bonded with the same 8-QNS ligand with a weak Au(I)…Au(I) interaction of 3.314 Å, which is also aggregated to form a tetranuclear supermolecule through a close intermolecular Au(I)…Au(I) contact of 3.133(1) Å. These complexes exhibit solid-state luminescence at 500-550 nm, where 1 and 2 can be tentatively attributed to ligand-to-metal charge-transfer transition (LMCT), and 3 and 4 possibly due to a metal-centered 5d(dσ*)→6p(pσ) transition.
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Hsu, Ming-Wei, and 許銘偉. "Pharmacokinetics of 4-Anilinofuro[2,3-b]quinoline Derivatives, New Synthetic Antitumor Compounds." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/55588372391863224163.
Full textAbstract:
碩士高雄醫學大學
藥學研究所碩士班
92
1-[4-(furo[2,3-b]-quinolin-4-ylamino)phenyl]ethanone (PK-L1) and its analogue, 1-[4-(3-chlorofuro[2,3-b]-quinolin-4-ylamino)phenyl]ethanone (PK- L4), both these 4-anilino[2,3-b]quinoline derivatives are presently new synthetic anti-tumor compounds. These two compounds, PK-L1 and PK-L4, are just different in one chlorine replacement on the structure. In vitro study showed that they could inhibit most tumor cell growth, including liquid and solid tumors. PK-L1 and PK-L4, however, were passed only through in vitro study and had yet neither related plasma drug analytical method nor in vivo study report. Therefore, the purpose of this study was to develop a plasma drug analytical method and explore the pharmacokinetics after administration of drug to normal rats. In this study, we used high performance liquid chromatography (HPLC) to determine the drug content in plasma. In addition, we explored the pharmaco- kinetics with two-compartment model after intravenous administration of PK-L1 at doses of 8.4, 4.2 and 2.1 mg/kg and PK-L4 at doses of 9.4, 4.7, 2.35 and 1.175 mg/kg. The results showed that the analytical method in this study provided both high accuracy and precision. Besides, after administration of drugs, both PK-L1 and PK-L4 represented non-linear pharmacokinetics at high doses above 4.2 and 4.7 mg/kg for PK-L1 and PK-L4, respectively; and both represented linear pharmacokinetics at lower doses, 2.1-4.2 mg/kg and 1.175-4.7 mg/kg for PK-L1 and PK-L4, respectively. In addition, the same molar doses of PK-L4, the compound with one chlorine replacement on the structure, produced higher area under the curve (AUC�~�_�V) and lower plasma clearance (Clp) but not the elimination half-life (t1/2 (��)). The mean t1/2 (��) values of PK-L1 and PK-L4 were 1.5 and 1.1 h, respectively.
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Ashmore, Jason Chemistry Faculty of Science UNSW. "The synthesis and inclusion chemistry of diheteroaromatic compounds." 2007. http://handle.unsw.edu.au/1959.4/40826.
Full textAbstract:
Diquinoline molecules have been shown previously to have interesting inclusion properties. Of the nine new, targeted molecules produced for this work, seven formed inclusion compounds, and their solid-state structures are discussed herein. Chapter 2 shows the effect that substituting a hydrogen atom with a chlorine atom has on the inclusion properties. This comes about because of the additional intermolecular attractions that are now possible, and a wider range of guest molecules is included as a result. A new homochiral aromatic 'swivel offset face-face (OFF)' interaction is observed. Chapters 3 and 4 deal with the effect of adding extra aromatic planes to the target molecules, two or four planes, respectively. Each of these host molecules formed dimeric host-host units that are extremely similar across all crystal structures. These dimers mainly employed aromatic edgeface (EF) interactions. Chapter 5 looks at the effect of combining the modifications described in Chapters 2-4, namely additional aromatic surfaces and atom substitution. The resulting host molecule specifically includes polyhalomethane guests. In addition, this host molecule formed two concomitant pseudo-dimorph compounds with chloroform-d. The diquinoline host molecule presented in Chapter 6 incorporated an isomeric central linker ring to the other compounds. Although only a single crystal structure could be obtained, 1H NMR spectroscopy experiments show other small aromatics may be included. The effect of electron donating chemical substituents was examined in Chapter 7. These compounds were found to be quite insoluble, and did not produce crystals suitable for X-ray analysis. The host molecules in Chapter 8 contain electron withdrawing nitro groups. The two isomeric compounds that act as inclusion hosts show quite different properties. One of these hosts forms a series of inclusion compounds with water, in which the site occupancy of the guest can range from 0-100% without change to the overall structure. All the X-ray structures described have been analysed in crystal engineering terms, and their supramolecular interactions described in detail.
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Nkosi, S'busiso Mfan'vele. "Synthesis of novel quinoline derivatives and their cytotoxicity in A549 lung cancer cells." Thesis, 2017. http://hdl.handle.net/10321/2675.
Full textAbstract:
Thesis submitted in fulfilment of the requirements for the Degree of Master's in Chemistry, Durban University of Technology, 2017.Quinoline and its derivatives represent an important class of nitrogen-containing heterocylces as they are useful intermediates in organic synthesis and possess a broad spectrum of biological activities, such as anti-asthmatic, anti-inflammatory and anti-malarial activity. Hence, synthesis of novel compounds with potent biological activities is important in medicine. Significant research is directed into the development of new quinoline based structures and new methods for their preparations. In the past, synthesis of complex molecules was accomplished by step-wise reaction. This was time consuming and yield was generally low. Nowadays, multi-component reactions (MCRs) are being used since three or more substrates can be reacted in a one-pot reaction. Therefore yields are higher and the reaction is more efficient. In this research investigation novel quinoline derivatives, using the multi-component reaction protocol, were synthesized. After characterization of the product by several spectroscopic techniques, the biological potential of these compounds were assessed using lung cancer cell lines, bacteria and molecular modeling in an enzymatic system. In the synthetic part of this study, the first step was the preparation of the starting compound 2- chloro-3-formyl quinoline for which the Vilsmeier-Haack cyclisation protocol was used. The cyclisation was carried out by combining DMF and POCl3 at 5°C to form an electrophile which then reacted in situ with N-phenylacetamide at 100ºC to afford 2-chloro-3-formyl quinoline in high yield (95%). This was followed by the synthesis of a series of novel quinoline derivatives in a MCR system comprising 2- chloro-3-formyl quinoline, malononitrile, aromatic amines and dimethyl acetylenedicarboxylate in the presence of a catalytic amount of triethylamine. Valuable features of this routine included high yields, extensive substrate range and straight forward procedures. Eight novel poly-functionalised dihydropyridine quinoline derivatives were synthesized, purified and characterized. The outline for the synthesis of poly-functionalised dihydropyridine quinoline derivatives is presented graphically in Scheme 1. Scheme 2 shows the eight compounds synthesized and used subsequently for further studies. . Step 1 CH3 a N O H CHO N Cl Step 2 CHO CN N Cl CN NH2 R O OCH3 b OCH3 O MeO2C MeO2C N Cl CN N NH2 R = m-CH3, o-OCH3, p-Cl, m,p-Cl, o-F, m-F, p-F R Reaction Conditions: a. DMF, POCl3 b. Et3N, EtOH Scheme 1: Graphical representation for the synthesis of poly-functionalised dihydropyridine quinoline derivatives The novel eight compounds were screened for their potential activity in lung cancer cell lines. A549 cells were incubated for 24 hours with a range of concentrations of each compound, in triplicate, in a micro-titre plate together with an untreated control. Each experiment was conducted twice on separate occasions; the results from the first set matched the repeated experiment. The cells were then incubated (37ºC, 5% CO2) with the MTT substrate for 4 hours. Thereafter all supernatants were aspirated and DMSO was added to the wells. Finally the optical density was measured at 570 nm at a reference wavelength of 690 nm with an ELISA plate reader. The net MTT dependant absorbance (optical density) of each sample was calculated by subtracting the average absorbance of the blank from the average absorbance of each sample. Data were represented as mean optical density plus or minus the standard deviation. Four of the synthesized compounds (A1-A8) were evaluated for their cytotoxicity activities. The anti-cancer assay indicated that poly-functionalised dihydropyridine quinoline compounds, A2, A3 and A4 have good potential as anti-cancer drugs. Among them, A2 and A4 proved to be dose dependent with A4 having the highest toxicity at 250 µM and A8 having the highest toxicity at 125, 250 and 500 µM, whereas A1, A5, A6 and A7 were not cytotoxic. O H3CO H3CO O N Cl CN NH2 O H3CO H3CO O N Cl CN N NH2 OCH3 O H3CO H3CO O N Cl CN N NH2 O H3CO H3CO O N Cl CN NH2 CH3 Cl A1 A2 A3 A4 O H3CO H3CO O N Cl CN N NH2 F O H3CO H3CO O N Cl CN N NH2 O H3CO H3CO O N Cl CN NH2 O H3CO H3CO O N Cl CN N NH2 F Cl F Cl A5 A6 A7 A8 Scheme 2: Structures of novel poly-functionalised dihydropyridine quinoline derivatives by MCRs Since molecular docking is a key tool in structural molecular biology and computer-assisted drug design, these compounds were subjected to molecular docking and the binding mode for the compounds, within the active site of the protein, was analyzed. Docking of A1 to Human mdm2 protein provided insights into the binding regions. Three hydrogen bonds were formed between GLU 25 (2.7 Å distance), LEU 27 (3.2 Å distance) and LEU 54 (3.2 Å distance) atoms with binding energy of -8.91 kcal/mol. Docking of A1 with Human mdm2 indicated the lowest binding energy thereby showing strong affinity of the ligand molecule with the receptor which has been stabilized by strong hydrogen bond interactions in the binding pocket. This confirms that A1 is a better inhibitor for E3 ubiquitin-protein ligase mdm2 than all the other compounds tested (A2-A8). Further, the eight novel poly-functionalised dihydropyridine quinoline derivatives were evaluated for their antibacterial activity. This was performed using the MABA method against three strains i.e. Gram negative; Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922) and Gram positive; Staphylococcus aureus (ATCC 29213) using the broth micro dilution method. Standard antibiotics (ciprofloxacin and nalidixic acid) were used as positive controls and DMSO was used as a negative control. The results obtained from the anti-bacterial assay showed that compounds A4, A7 and A8 have high activity, whereas A2 and A3 showed poor activity against all the tested bacterial strains. Compound A6 showed no activity against S. aureus and E. coli.
M
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"Metallation of 8-methylquinoline." Chinese University of Hong Kong, 1993. http://library.cuhk.edu.hk/record=b5887206.
Full textAbstract:
by Lawrence Tin-chi Law.Thesis (M.Phil.)--Chinese University of Hong Kong, 1993.
Includes bibliographical references (leaves 96).
acknowledgements --- p.iii
ABSTRACT --- p.iv
CONTENTS --- p.v
ABBREVIATION --- p.vii
Chapter CHAPTER I --- METALLATION OF 8-METHYLQUINOLINE
Chapter 1.1 --- INTRODUCTION --- p.1
Chapter 1.1.1 --- A Brief Review of Metal-Alkyl Chemistry --- p.1
Chapter 1.1.2 --- General Considerations --- p.2
Chapter 1.1.3 --- 8-Methylquinoline as Ligand Precursor --- p.8
Chapter 1.1.4 --- Metallations by Organolithium Compounds --- p.9
Chapter 1.1.5 --- Other Methods for Metallations --- p.16
Chapter 1.1.6 --- Aim of the Present Work --- p.21
Chapter 1.2 --- RESULTS AND DISCUSSION --- p.24
Chapter 1.2.1 --- Reactions of 8-Methylquinoline with Organolithium Reagents --- p.26
Chapter 1.2.2 --- Synthesis of Grignard Reagent --- p.35
Chapter 1.2.3 --- Attempted Metal-Halogen Exchange Reaction at Low Temperature --- p.39
Chapter 1.2.4 --- Metallation of 8-methylquinoline by Lithium Diisopropylamide --- p.40
Chapter 1.3 --- EXPERIMENTAL FOR CHAPTER I --- p.43
Chapter 1.4 --- REFERENCES FOR CHAPTER I --- p.53
Chapter CHAPTER II --- SYNTHESIS AND CHARACTERISATION AND STRUCTURE OF SOME MAIN GROUP 14 ALKYLS
Chapter 2.1 --- INTRODUCTION --- p.58
Chapter 2.1.1 --- General Aspects of Group 14 Organometallic Compounds --- p.58
Chapter 2.1.2 --- Group 14 Organometallic Confounds --- p.59
Chapter 2.1.3 --- Subvalent Group 14 Metal Alkyls --- p.63
Chapter 2.2 --- RESULTS AND DISCUSSION --- p.67
Chapter 2.2.1 --- Synthesis of Five Co-ordinated Tin (IV) Compound --- p.67
Chapter 2.2.2 --- Molecular Structure of [Sn{8-(CHSiMe3)C9H6N}Ph2Cl] --- p.70
Chapter 2.2.3 --- Synthesis of Group 14 Subvalent Metal Complexes --- p.74
Chapter 2.3 --- EXPERIMENTAL FOR CHAPTER II --- p.76
Chapter 2.4 --- REFERENCES FOR CHAPTER II --- p.79
Chapter CHAPTER III --- SYNTHESIS AND CHARACTERISATION OF SOME GROUP 12 (ZINC AND CADMIUM) METAL DIALKYLS
Chapter 3.1 --- INTRODUCTION --- p.81
Chapter 3.1.1 --- A General Aspect of Group 12 Organometallics --- p.81
Chapter 3.2 --- RESULTS AND DISCUSSION --- p.88
Chapter 3.2.1 --- Synthesis of Group 12 Organometallic Confounds --- p.88
Chapter 3.2.2 --- Molecular Structure of [Cd{8-(CHSiMe3)C9H6N}(tmeda)Cl] --- p.91
Chapter 3.3 --- EXPERIMENTAL FOR CHAPTER III --- p.93
Chapter 3.4 --- REFERENCES FOR CHAPTER III
APPENDIX I
Chapter 1. --- GENERAL PROCEDURES --- p.97
Chapter 2. --- PHYSICAL AND ANALYTICAL MEASUREMENTS --- p.100
APPENDIX II
LIST OF SELECTED 1H NMR SPECTRA --- p.101
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Makhanya, Talent Raymond. "Synthesis of bisquinolines through conventional and unconventional energy sources." Thesis, 2011. http://hdl.handle.net/10321/715.
Full textAbstract:
Thesis submitted in fulfilment of the requirements for the Degree of Master of Technology: Organic Chemistry, Durban University of Technology, 2011.Malaria, the most prevalent parasitic disease, is considered a neglected disease owing to insufficient research and development in synthesis and therapy worldwide. Therapy failures are frequent and are due to a variety of factors such as the intrinsic characteristics of the disease, conditions of transmission, and the difficult control of spreading through tropical areas. Primary factors are the complexity of the parasite life cycle and the development of drug resistance. Another critical factor is the increasing number of immune-compromised patients that suffer from malaria and human immunodeficiency virus (HIV) co-infections. Most of the drugs currently available to treat malaria are quinoline derivatives modelled on the quinine molecule, found in the bark of Cinchona trees. Over the last 50 years the use of quinine has declined owing to the development of synthetic 4-aminoquinolines such as chloroquine. However, the malaria parasite is rapidly becoming resistant to the drugs currently available. Recently bisquinoline compounds were found more potent than chloroquine against both chloroquine-sensitive and resistant strains of malaria; this improved efficacy and prompted an increased interest in the design of these anti-malarial drugs. Although several synthetic methods are available to synthesise bisquinolines, we report the synthesis of bisquinolines from simple, readily available and cost- effective starting compounds. The synthesis was accomplished in four reaction steps using the Claisen condensation, Vilsmeir-Haack reaction, formation of a Schiff base and thermal cyclization, sequentially. We used a conventional energy source and microwave irradiation for the synthesis, wherever possible, of 2, 4-dichloro-3, 4'-biquinoline and 2, 4-dichloro-7'-methoxy-3, 4'-biquinoline. In the first step, 3-acyl-2, 4-dihydroxyquinoline is synthesised from an equimolar mixture of methyl-2-aminobenzoate and ethyl acetoacetate by microwave irradiation for 3 minutes; the yield is 90 % whereas by 6 hours refluxing the yield is 75 %. This is followed by the synthesis of 3-chloro-3-(2,4-dichloroquinolin-3yl) acrylaldehyde, by combining DMF and POCl3 at 00C to form the electrophile which reacts with 3-acyl-2,4-dihydroxyquinoline under microwave irradiation for 5 minutes; the yield is 65 % whereas by 6 hours refluxing the yield is 50 %. In the next step, several protocols to prepare a Schiff base 3-chloro-3-(2, 4-dichloroquinolin-3-yl) allylidene aniline are investigated with the best yield of 75% obtained by microwave irradiation for 5 minutes. Subsequently three aniline derivatives viz, 4-methoxyaniline, 4-chloroaniline and 4-methylaniline, are used as substrate to prepare 3-chloro-3-(2,4-dichloroquinolin-3-yl) allylidene-4-methoxyaniline, 3-chloro-3-(2 ,4-dichloroquinolin-3-yl) allylidene-4-methylaniline and 3-chloro-3-(2, 4-dichloroquinolin-3-yl) allylidene-4-chloro aniline at 68, 78 and 64 % yield, respectively. In the final step, 2, 4-dichloro-3, 4'-biquinoline is prepared; several methods were investigated, however, the best yield is 24 % which is obtained under alkaline conditions in the presence of K2CO3 and DMF by microwave irradiation for 10 minutes. The 2, 4-dichloro-7'-methoxy-3, 4'-biquinoline derivative is also prepared in 18 % yield under the same alkaline conditions. The outline of the total synthesis of bisquinoline is presented graphically below.
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Lesenyeho, Lehlogonolo Godfrey. "Palladium-catalyzed heteroannulation of 2-ARYL- 3-IODO-4-(Phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-ARYL-3-iodoquinolines." Diss., 2010. http://hdl.handle.net/10500/3970.
Full textAbstract:
The previously described 2-aryl-4-chloro-3-iodoquinolines were prepared following literature procedure and in turn converted to the corresponding hitherto unknown 2-aryl-3-iodo-4-(phenylamino)quinoline derivatives using aniline in refluxing ethanol. These 2-aryl-3-iodo-4-(phenylamino)quinolines were reacted with allybromide in ethanol at room temperature to afford 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives. The 2-aryl-3-iodo-4-(phenylamino)quinoline and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were subjected to metal-catalysed carbon-carbon bond formations. Palladium(0)-copper iodide catalysed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinoline with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single step operation. On the other hand, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo palladium-catalysed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines. All new compounds were characterized by using a combination of NMR (1H and 13C), IR, mass spectroscopic techniques as well as elemental analysis.Chemistry
MSc. (Chemistry)
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Chiou, Zan Wei, and 邱贊瑋. "Pharmacological studies of pyrazolo[4,3-c]quinoline compound in human neutrophils." Thesis, 2019. http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107CGU05553009%22.&searchmode=basic.
Full text
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Chou, Chein-an, and 周建安. "Complexation of camphor sulfonic acid to affect the emission behavior of organic compound and polymer with quinoline moiety." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/09652709812360188133.
Full textAbstract:
碩士國立中山大學
材料與光電科學學系研究所
98
Many chromophoric organics and polymers are highly emissive in their dilute solutions but become weakly luminescent in the high concentration and solid film states due to the induced π−π interactions of the intimately-contact chromophores. Therefore, it is practically important to develop fluorescent organic and polymeric materials with enhanced emission in their aggregated states (so called aggregated-induced emission, AIE). In this study, organic compound 2,4-diphenylquinoline (DPQ) with inherent quinoline ring and polymeric poly(vinyl diphenylquinoline) (PVQ) with pendant quinoline group were prepared and their AIE-phenomena were characterized. To prove the reported point that restriction of intramolecular rotation (RIR) is the main cause for AIE effect, DPQ and PVQ were further incorporated with organic strong acid of camphorsulfonic acid (CSA). Through the favorable acid-base interaction between the sulfonic acid in CSA and the nitrogen atom of the quinoline ring in DPA (or CSA), ionic complex of DPQ-CSA (and PVQ-CSA) was easily prepared and their response toward AIE properties were studied. Through the enhanced RIR by the complexation of bulky CSA with the central quinoline ring, the resulting DPQ-CSA (and PVQ-CSA) complex was proved to have better AIE-effect compared to the pristine DPQ (and PVQ). RIR mechanism can be indirectly proved in this case. We study the AIE on micelle topics of the block copolymer. We choose the poly(styrene-block-tertbutylstyrene) (PS-b-PBS) as our block copolymer. To synthesize the PS-b-PBS, we can successfully get the new block copolymer PVQ-b-PBS. PVQ-b-PBS was similarly blended with the CSA. In the block copolymer micelles, choose the selective solvent to get the different micelles and observe the diverse on the luminescence. Finally, we analyzed compositions and conformations by atomic force microscopy (AFM) and transmission electron microscopy (TEM).