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Mohamadi, Shahrzad. "Electrochemical screening of biological membrane active compounds." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/8619/.
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Interactions of biomembrane-active compounds with phospholipid monolayers on microfabricated Pt/Hg electrodes in an on-line high throughput flow system are demonstrated by recording capacitance current peak changes in rapid cyclic voltammograms (RCV). Detection limits of the compounds' effects on the layer have been estimated from the data. Compounds studied include steroids, polycyclic aromatic hydrocarbons, tricyclic antidepressants, tricyclic phenothiazines pyridinium compounds, spiperone and spiperone analogues and a range of serotonin and dopamine receptor ligands. The results show that the extent and type of interaction depends on the: - (a) presence and number of aromatic rings and substituents, (b) presence and composition of side chains and, (c) molecular shape. Interaction is only indirectly related to compound hydrophobicity. For a selection of tricyclic antidepressants and tricyclic phenothiazines the detection limit in water is related to their therapeutic normal threshold. The sensing assay has been tested in the presence of humic acid as a potential interferent and in a tap water matrix. It was subsequently tested in a natural water matrix. The system can be applied to the screening of putative hazardous substances allowing for early detection thereof in the water supply. The measurements are made in real time which means that potentially toxic compounds are detected rapidly in <10 minutes per assay. This technology will contribute greatly to environment safety and health.
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Esmati, Nasim. "Synthesis of Biologically Active Compounds via Multicomponent Reactions and Evaluation of Their Biological Activities." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1525897360405194.
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Boukes, Gerhardt Johannes. "The in vitro biological activities of three Hypoxis species and their active compounds." Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/1228.
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The African potato is used as an African traditional medicine for its nutritional and medicinal properties. Most research has been carried out on H. hemerocallidea, with very little or nothing on other Hypoxis spp. The main aim of this project was to provide scientific data on the anticancer, anti-inflammatory and antioxidant properties of H. hemerocallidea, H. stellipilis and H. sobolifera chloroform extracts and their active compounds. The hypoxoside and phytosterol contents of the three Hypoxis spp. were determined using TLC, HPLC and GC. H. hemerocallidea and H. sobolifera chloroform extracts contained the highest amounts of hypoxoside and β-sitosterol, respectively. For the anticancer properties, cytotoxicity of the Hypoxis extracts and its purified compounds were determined against the HeLa, HT-29 and MCF-7 cancer cell lines (using MTT), and PBMCs (using CellTiter-Blue®). H. sobolifera had the best cytotoxicity against the three cancer cell lines, whereas H. stellipilis stimulated HeLa and HT-29 cancer cell growth. IC50 values of hypoxoside and rooperol were determined. DNA cell cycle arrest (using PI staining) occurred in the late G1/early S (confirmed by increased p21Waf1/Cip1 expression) and G2/M phases after 15 and 48 hrs, respectively, when treated with Hypoxis extracts and rooperol. H. sobolifera and rooperol activated caspase-3 and -7 (using fluorescently labelled antibodies) in HeLa and HT-29 cancer cells, and caspase-7 in MCF-7 cancer cells after 48 hrs. Annexin V binding to phosphatidylserines in rooperol treated U937 cells confirmed early apoptosis after 15 hrs. The TUNEL assay showed DNA fragmentation in the three cancer cell lines when treated with H. sobolifera and rooperol for 48 hrs. A shift pass the G2/M phase has led to the investigation of endoreduplication, which was confirmed by cell/nucleus size, and anti-apoptotic proteins (Akt, phospho-Akt, phospho-Bcl-2 and p21Waf1/Cip1). U937 cell differentiation to monocyte-macrophages was optimized using PMA and 1,25(OH)2D3, which was confirmed by morphological and biochemical changes. For the anti-inflammatory properties, Hypoxis extracts and rooperol significantly increased NO production in monocyte-macrophages (pre-loaded with DAF-2 DA) and phagocytosis of pHrodoTM E. coli BioParticles®. The treatments had no effect on COX-2 expression in monocyte-macrophages. The phytosterols significantly increased IL-1β and IL-6 secretion xv (using the FlowCytomix Multiplex human Th1/Th2 10plex Kit I) in the PBMCs of one donor. For the antioxidant properties, Hypoxis extracts and rooperol significantly increased ROS production in undifferentiated and differentiated U937 cells, which were pre-loaded with DCFH-DA. Hypoxis extracts and purified compounds had ferric reducing activities, but only rooperol had ferric reducing activities significantly greater than ascorbic acid. β-sitosterol, campesterol and cholesterol significantly increased SOD activity in Chang liver cells, while H. stellipilis, H. sobolifera and rooperol decreased SOD activity. Anticancer, anti-inflammatory and antioxidant properties of the Hypoxis extracts may be attributed to the β-sitosterol content, because Hypoxis chloroform extracts contained very little or no hypoxoside. Unidentified compounds, and synergistic and additive effects of the compounds may have contributed to the biological effects. This study confirms previous reports that rooperol is the active compound. Results provide scientific data on the medicinal properties of one of the most frequently used medicinal plants in South Africa.
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Karpf, Ditte Maria. "Intestinal lipoprotein secretion and lymphatic transport of poorly aqueous soluble compounds /." Kbh. : The Danish University of Pharmaeutical Sciences, Department of Pharmaceutics, 2005. http://www.dfuni.dk/index.php/Previous_PhD_Defences_2005/1735/0/.
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Salgado, Ricardo Manuel Nunes. "The removal of xenobiotic compounds from wastewater through the use of biological processes and advanced oxidation technologies." Doctoral thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/6918.
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Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Química e Bioquímica pela Universidade Nova de Lisboa, Faculdade de Ciências e TecnologiaFCT/MCTES projects PTDC/AMB/65702/2006 and SFRH/PROTEC/49449/2009 and SFRH/BPD/30800/2006 ; COST Action 636
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Geller, Fabiana Cristina [Verfasser]. "Isolation, Structure Elucidation and Biological Investigation of Active Compounds in Cordia americana and Brugmansia suaveolens / Fabiana Cristina Geller." München : Verlag Dr. Hut, 2011. http://d-nb.info/1011441357/34.
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Geller, Fabiana [Verfasser]. "Isolation, Structure Elucidation and Biological Investigation of Active Compounds in Cordia americana and Brugmansia suaveolens / Fabiana Cristina Geller." München : Verlag Dr. Hut, 2011. http://nbn-resolving.de/urn:nbn:de:101:1-20110503905.
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Seotsanyana-Mokhosi, Itumeleng. "Photosensitizing properties of non-transition metal porphyrazines towards the generation of singlet oxygen." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1006086.
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Metallophthalocyanine complexes containing non-transition metals are very useful as sensitizers for photodynamic therapy, a cure for cancer that is based on visible light activation of tumour localized photo sensitizers. Excited sensitizers generate singlet oxygen as the main hyperactive species that destroy the tumour. Water soluble sensitizers are sought after for the convenience of delivery into the body. Thus, phthalocyanine (pc), tetrapyridinoporphyrazines (tppa) and tetramethyltetrapyridinoporphyrazines (tmtppa) with non-transition central metal atoms of Ge, Si, Sn and Zn were studied. First was the synthesis of these complexes, followed by their characterisation. The characterisation involved the use of ultraviolet and visible absorption spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, electrochemical properties and elemental analysis. Photochemical properties of the complexes were then investigated. Photolysis of these macrocycles showed two processes; -reduction of the dye and photobleaching, which leads to the disintegration of the conjugated chromophore structure of the dye. Photobleaching is the reductive quenching of the excited state of the sensitizers. The intensity of the quenching decreased progressively from tmtppa, tppa to pc metal complexes with photobleaching quantum yields, 6.6 x 10.5⁻¹, 1.8 x 10.5⁻¹ and 5.4 x 10⁻⁶ for Zntmtppa, Zntppa and Znpc, respectively. Efficiency of singlet oxygen sensitization is solvent dependent with very different values obtained for the same compound in different solvents, for example, 0.25 and 0.38 were observed as singlet oxygen quantum yields for Gepc complex in DMSO and DMF respectively. In DMSO the efficiency of ¹O₂ generation decrease considerably from pc to tppa and finally tmtppa. In water Getmtppa exhibits much higher singlet oxygen quantum yield, hence promising to be effective as a sensitizer for photodynamic therapy.
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Sbardella, Luca. "Evaluation and comparison of advanced treatment technologies to enhance the removal of pharmaceutical active compounds from wwtp secondary effluent." Doctoral thesis, Universitat de Girona, 2019. http://hdl.handle.net/10803/668690.
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The presence of several pharmaceutical active compounds (PhACs) in water bodies has garnered increasing attention and worldwide concern. The effluents from wastewater treatment plants (WWTPs) are one of the main sources of PhACs in aquatic environments. Advanced tertiary treatments are required to improve the quality of WWTP effluents discharged into sensitive receiving water bodies. This thesis has focused on biological activated carbon coupled with ultrafiltration (BAC-UF) and UV-C activated peroxydisulfate and peroxymonosulfate (UV/PDS and UV/PMS). The BAC-UF technology has been evaluated at pilot-scale during one year of operation, assessing the removal of 15 PhACs at environmentally relevant concentration. With respect to UV/PDS and UV/PMS technologies, they were preliminarily assessed with a set of lab-scale experiments and then, validated at pilot-scale simulating real operating conditions. Finally the comprehensive evaluation of these advanced treatment technologies identified some of the practical factors limiting the potential application of BAC-UF, UV/PDS and UV/PMS technologies.La presencia de varios compuestos activos farmacéuticos (PhACs) en las masas de agua ha ganado una atención creciente y preocupación mundial. Los efluentes de las depuradores son una de las principales fuentes de PhAC en entornos acuáticos. Se requieren tratamientos terciarios avanzados para mejorar la calidad de los efluentes de las depuradoras que abocan en masas de agua receptoras sensibles. Esta tesis se focaliza en la tecnologias de carbón activo biológico combinado con la ultrafiltración (BAC-UF) y el peroxidisulfato y el peroximonosulfato activados por UV-C (UV/PDS y UV/PMS). La tecnología BAC-UF se ha evaluado a escala piloto durante un año de operacion, evaluando la eliminación de 15 PhACs. Con respecto a UV/PDS y UV/PMS, se evaluaron preliminarmente a escala de laboratorio y luego se validaron a escala piloto, simulando condiciones reales de operación. Finalmente, la evaluación integral de estas tecnologías de tratamiento avanzadas identificó algunos de los factores prácticos que limitan la aplicación potencial de las tecnologías BAC-UF, UV/PDS y UV/PMS.
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Mohammed, Warda. "Optimizing Sample Dissolution Methods of Low Water Soluble Intermediate Organic Compounds to Support Environmental Risk Assessment during Active Pharmaceutical Ingredient Manufacturing." Thesis, Örebro universitet, Institutionen för naturvetenskap och teknik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-93416.
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This project focus on investigating the dissolution of low water-soluble intermediate organic compounds called active pharmaceutical ingredients (API) and organic substances that are manufactured by a pharmaceutical company, Cambrex Karlskoga in Sweden. Several dissolution methods were used and evaluated using methods including total organic carbon (TOC), chemical oxygen demand (COD), biochemical oxygen demand (BOD) and Microtox toxicity test. The selection of solvents were based on previous studies and specifications from the Swedish Institute of Standards, SIS.The performance of eight solvents for different organic substances were evaluated using the above mentioned methods. Solvents that are highly volatile and have low solubility in water were excluded. Therefore, dimethyl sulfoxide (DMSO), dimethylformamide (DMF) and Pluronic F-68, that had highest water solubility, low acute toxicity and not degradable by microorganisms, were further used to dissolve four organic substances. Furthermore, DMSO and DMF were then also used to dissolve four censored chemicals with addition of physical treatment and solvent mixtures (DMF:DMSO with ratio 1:2).Results from each method were discussed and statistical tests were also performed in order to compare different dissolution methods. In addition, quality control and quality assurance were made in order to ensure the quality of measured values from analytical methods. Four organic substances were dissolve in DMSO, DMF and Pluronic F-68 with dissolution ≥79% using six ratios of DMSO and DMF and five ratios of Pluronic F-68 which were analyzed using TOC. Physical treatment increased dissolution of two APIs with 40%. Using BOD, para-aminobenzonic acid (PABA) and 5-nitroisophthalic acid (5-NIPA) had values higher than the guideline values, which indicate high biodegradability of these organic substances. PABA, 5-NIPA and bupivacaine base were acute toxic where PABA showed EC50 values of 27.9 mg/L using DMSO and 36.0 mg/L using DMF, and EC50 values of 5-NIPA were 102 mg/L using DMSO and 84.0 mg/L using DMF, and bupivacaine base had EC50 value of 174 mg/L using solvent mixture (DMF:DMSO with ratio 1:2). With increasing amount of Pluronic F-68, 5-NIPA had increased values of EC50, thereby Pluronic F-68 was not appropriate to use.In conclusion, DMSO and DMF were most appropriate solvents to use in order to dissolve APIs and organic substances with analyte: DMSO ratio of 1:0.5 and analyte: DMF ratio of 1:0.25. In addition, physical treatment could be used in order to increase dissolution of the APIs.
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Omar, Muhammad Nor bin. "Synthesis of biologically active compounds." Thesis, Liverpool John Moores University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343121.
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Burnell, Erica Sinead. "Synthesis of biologically active compounds." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/synthesis-of-biologically-active-compounds(a009591b-d439-4ff7-9e6f-36199a33e7c8).html.
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Part 1 describes the synthesis of (2S,3S,4R,5R)-5-(6-(((7-bromo-2-(dimethylamino)-4-((3-methylisoxazol-5-yl)methoxy)benzo[d]oxazol-5-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide, a selective A3 adenosine receptor agonist, and one of a number of adenosine analogues designed by Muscagen Ltd. with the purpose of treating cardiac ischaemia. The target compound was derived from a condensation of the known modified adenosine, (3aS,4S,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-N,2,2-trimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide with 5-(aminomethyl)-7-bromo-N,N-dimethyl-4-((3-methylisoxazol-5-yl)methoxy) benzo[d]oxazol-2-amine. The benzoxazole amine fragment was synthesised from commercially available nitroresorcinol. Part 2 details the synthesis of two potential M1 muscarinic receptor agonists -(3aS*,7R*,7aR*)-3,7-dibenzyl-3a-cyclobutylhexahydro-2H-pyrano[3,4-d]oxazol -2-one and (3aSR,7RS,7aRS)-3,5,7-tribenzyl-3a-cyclobutylhexahydrooxazolo[4,5 -c]pyridin-2(3H)-one, part of a series of compounds designed by Muscagen Ltd. for the treatment of Alzheimer’s disease. Both targets were synthesised from the known carbamate intermediate, (S)-benzyl (1-((tert-butyldimethylsilyl) oxy)-2-cyclobutylbut-3-en-2-yl)carbamate, which was available from commercially available cyclobutyl carboxylic acid. Part 3, the final part, describes efforts made towards the total synthesis of the natural product, phomactin A, a desirable target for its biological activity as a platelet activating factor antagonist, in addition to its structural complexity. Building on previous research carried out in the group, advanced intermediate (2S*,3R*,5R*,12S*,13R*,15R*,E)-16-(hydroxymethyl)-5,9,12,13-tetramethyl-4-oxatricyclo[10.3.1.03,5]hexadeca-1(16),8-diene-2,15-diol was synthesised from a macrocyclic intermediate tert-butyldiphenyl (((1S*,2S*,4E,8E,10R*,12S*,14R*) -1,4,8,14-tetramethyl-15-methylene-2-(phenylsulfonyl)-10-((2-(trimethylsilyl) ethoxy)methoxy)bicyclo[9.3.1]pentadeca-4,8-dien-12-yl)oxy)silane.
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Nachman, J. "Structural studies on biologically active compounds." Thesis, University of Cambridge, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356662.
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Birch, D. J. "The synthesis of biologically active compounds." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233498.
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Wilson, Jennifer M. "Synthesis of biologically active heterocyclic compounds." Thesis, University of Glasgow, 2007. http://theses.gla.ac.uk/45/.
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More than 11 million people worldwide are diagnosed with cancer every year. New cancer drugs are required that are more effective and selective. Nitrogen mustard alkylating agents crosslink DNA inhibiting transcription and replication. Use of the mustard pharmacophore as part of a macrocycle allows metal complexation and produces a prodrug. Hypoxic tumour cells have increased concentrations of reductase enzymes which could lead to reduction of the complex in situ and release of a cytotoxic drug. Human African Trypanosomiasis is commonly known as Sleeping Sickness and affects over 36 countries of sub-Saharan Africa. It is transmitted to humans by the tsetse fly which carries the parasitic subspecies Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Any compounds synthesised would also be tested to assess their potential as anti-parasitic agents. Parker synthesised a range of polyazamacrocycles. Testing of compound A in vitro gave highly efficient DNA crosslinking activity. Copper complexes were formed of the macrocycles and B was found to be 24 times more toxic against hypoxic cells than oxic cells thus exploiting tumour hypoxia and creating a selective drug. Jones synthesised a range of oxaazamacrocycles such as C which when tested in vitro exhibited comparable cross-linking activity to the azamacrocycles although it proved impossible to synthesise the corresponding copper complexes. It was decided to vary the leaving group on the alkylating arms to see if the DNA crosslinking results could be improved. Eight carbamates and the corresponding copper complexes were synthesised. The R-groups were alkyl and aromatic. Anti-cancer DNA crosslinking and hypoxia selectivity results were disappointing however, a number of compounds displayed significant activity when tested against T. brucei. A range of thiaazamacrocycles would complete the set of heteroatom-containing macrocycles (N, O, S) and might produce good DNA crosslinking results. It might also be possible to synthesise the corresponding copper complexes producing prodrugs. Six thiaazamacrocycles were synthesised and 2-hydroxyethyl arms were attached. However it proved impossible to isolate the desired alkylating agents with the 2-chloroethyl arms. In the body, the p53 protein activates the transcription of specific genes. In healthy cells, the levels of p53 have to be kept to a minimum to allow the normal running of the cell, e.g. growth and replication. This function is carried out by the HDM2 protein, which forms an auto-regulatory feedback loop with p53. In some tumours, the p53 function is disrupted due to genetic mutations of p53. However other tumours possess ‘wild type’ p53 – this type of p53 has lost the ability to respond to oncogenic stress due to over-expression of HDM2. Drugs that inhibit HDM2 should cause stabilisation of p53 and induce apoptosis in cancer cells. A small library of 5-deazaflavins were synthesised and biologically tested producing some interesting biological results.
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Whapham, Catherine. "Biologically-active compounds in seaweed extracts." Thesis, University of Portsmouth, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310473.
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Bandini, Elisa <1966>. "Biologically Active Compounds Via 2-Aza-1,3-Dienes." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/476/.
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Mutlu, Esra. "Synthetic and Analytical Studies of Biologically Active Compounds." Thesis, University of Newcastle upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489838.
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first part of the project aimed to access tetralone intermediates required for the benzo[f]quinazoline inhibitors of thymidylate synthase. The project focussed sibility ofusing the intramolecular Buchner reaction to devise a short route from ailable starting materials. Hence, this route to the tetralones was via Rh(II) decomposition of precursor diazoketones. The synthesis of benzoquinazolines bus routes was relatively long, problematical and not cost effective. It was found of diazoketones with Rh(II) catalysis lead to the desired tetralones in e yields (Scheme 1). 1. Synthesis of tetralones via intramolecular Buchner reaction. .e objective in the second part of the project was to develop new approaches to leosides'. The introduction of the thio functionality in place of oxygen into the gar moiety of a nucleoside is a strategy for obtaining novel, potent anticancer and agents. The elaboration of commercially available chiral starting materials into s is the approach we used.
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Askew, Stuart Clive. "Some studies of biologically active S-nitrosothiols." Thesis, University of St Andrews, 1995. http://hdl.handle.net/10023/15189.
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S-nitrosothiols are effective NO-donating drugs which can elicit vasodilation of vascular tissue and disaggregate or inhibit the aggregation of platelets in blood. The chemistries of two S-nitrosothiols, S-nitroso-N-acetyl-DL-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) have been investigated in an attempt to identify the chemical and physiological mechanisms which underlie their biological actions as vasodilators and modulators of platelet behaviour. Although SNAP and GSNO have been found to be susceptible to decomposition by similar chemical mechanisms, such as by thermal and photochemical means, evidence is presented to suggest that they are both capable of NO transfer to other thiol containing compounds such as cysteine. This produces a very unstable S-nitrosothiol, S-nitrosocysteine, which readily produces NO. However, they can both be decomposed by different, distinctive mechanisms. Metal ion catalysis by copper is shown to greatly accelerate the decomposition of SNAP, but has little effect on GSNO. Instead, NO release from GSNO is effected by enzymatic cleavage of the glutamyl-cysteinyl peptide bond by the enzyme glutamyl transpeptidase (γ-GT). The resulting S-nitrosothiol, S-nitrosocysteinylglycine, would be expected to be more susceptible to release of NO by metal (copper) ion catalysis. It is concluded that transnitrosation (NO-transfer) between thiol groups, or enzymatic cleavage are obligatory steps in the mechanism of NO release from GSNO, whereas SNAP requires only the presence of trace amounts of metal ions like copper to effect this process. The different modes of NO production may go some way towards explaining the different physiological effectiveness of these S-nitrosothiols as vasodilators and inhibitors of platelet aggregation.
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Begum, Lovely. "The synthesis of fluorinated analogues of biologically active compounds." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343327.
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Vydrová, Lucie. "Využití separačních metod pro studium biologicky aktivních látek ve vodách." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2011. http://www.nusl.cz/ntk/nusl-233344.
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Pharmaceuticals are biological active compounds with different functional groups, physico-chemical and biological properties. These chemical compounds are called as “new contaminants” which cumulate in various environmental components. These contaminants input to environment from industrial processes, hospitals and health care institutions or household sources and these pollutants can to negatively interact with environmental components. Pharmaceuticals are separated according to structure and their effects to live organisms. On the basis of drug consumption in Czech Republic the non-steroidal anti-inflammatory drugs are the most using pharmaceuticals, because these drugs can be obtain without prescriptions. The choosing analgesics for study were monitored in waste water from waste waters treatment plant (WWTP Brno – Modřice) and in surface water from two sampling sites of river Kretinka. Pharmaceuticals were monitored in surface waters in Czech Republic, in Scotland (river Thurso) and in Taiwan (river Erren, Agongdian, Yanshuei and canal of Tainan) Solid phase extraction (SPE) is used for extraction of study pharmaceutical from water system. The high performance liquid chromatography (HPLC) with diode array detection or mass spectrometry was used for determination of drugs in surface waters from Czech Republic. The water samples from Scotland and Taiwan were analysed and the high performance liquid chromatography with mass spectrometry (HPLC/MS) was used for determination of pharmaceuticals. The method of HPLC/MS enables the determination of study compounds in the very low range of concentrations (ng ? l-1). All monitored pharmaceuticals were identified and quantified in water samples from river Kretinka in Czech Republic, river Thurso (Scotland) and rivers Erren, Agongdian, Yanshuei and canal of Tainan in Taiwan and the obtained data were compared.
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Wickens, Kristen M. "A search for biologically active compounds in Acacia (Mimosaceae) species." Curtin University of Technology, Department of Environmental Biology, 2003. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=15212.
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Indigenous Australians were also known to use plants for medicinal purposes. For thousands of years, Indigenous Australians have used native plants as a source of medicinal agents. Some tribes living in Central Australia still, to this day, prefer to use traditional medicines in favour of the more common and readily available western medicines. A number of plant species endemic to Australia are listed in various Aboriginal pharmacopoeias, with approximately one-third of those species belonging to two genera, Acacia and Eremophila. Of the 1100 recognised species of Acacia, approximately 900 occur in Australia. At least thirty of these species were utilised by the Indigenous Australians as a source of medicine. Extracts of 8 Acacia species were screened using four frontline bioassays. These were the brine shrimp lethality test, the crown gall tumour assays, the disc diffusion antibiotic assay and the seed germination test to determine if any of the species were biologically active. Of all the species screened, Acacia pruinocarpa showed the most promise. The species demonstrated significant activity at concentrations at low as 3.7ppm, which is well below the standard 400ppm exhibited by potassium dichromate (Sam, 1993). Acacia adsurgens and A. dictophleba were the next two promising species exhibiting activity at concentrations of 16.12ppm and 37ppm respectively. This was a trend that was also observed in the Lettuce seed germination test for allelopathy with these three species showing the most promise. Interestingly the potency of A. pruinocarpa extract decreased significantly when it was re- screened after being put through a polyamide column. It can therefore be suggested that as tannins are removed by the polyamide column, the biological activity exhibited by A. pruinocarpa is a result of the tannin content in the species (2%), although more testing is required.Both A. pruinocarpa and A. adsurgens showed promise as anti-tumour activity when used in the Crown Gall Tumour Assay (CGTA). Acacia pruinocarpa and A. adsurgens both exhibited significant activity when compared to the control producing inhibition percentages of 31% and 37% respectively. Surprisingly, only one of the Acacia species tested inhibited pathogenic growth when tested on the common pathogens Staphylococcus aureus, Streptococcus pyogens and Candida albicans. Acacia bivenosa was the only species to exhibit any activity when tested on the pathogens. This activity, however is not considered to be significant, as the species was only active against one of pathogens tested, Staphylococcus aureus. In order to be considered to be significant, a species must be active against two or more pathogens. It is however, worthy of further evaluation. Acacia species are among the large number of plants that have long been regarded sources of biological activity. This study was guided by the indigenous use of Acacia species as sources of medicine, which led to the use of front-line bioassays. All of the species tested exhibited some form of biological activity. Acacia pruinocarpa demonstrated the most promise as a source of novel biologically active compounds exhibiting activity at very low concentrations. Such compounds have not been determined as it was outside the scope of this study to identify the active constituents of this species. However, it has been suggested that tannins are responsible for eliciting some of the activity observed in A. pruinocarpa. All of the species screened in this study are worthy of further evaluation. The bioassays used in this study are good examples of front-line bioassays. All of the tests used in the study fulfil the criterion, which defines a good test.
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Witherington, Jason. "Novel synthetic methods enabling the construction of biologically active compounds." Thesis, University of Reading, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386942.
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Mosconi, Elisa <1981>. "Stereoselective synthesis of heterocycles as intermediates of biologically active compounds." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3432/.
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The aim of this thesis was to investigate the synthesis of enantiomerically enriched heterocycles and dehydro-β-amino acid derivatives which can be used as scaffolds or intermediates of biologically active compounds, in particular as novel αvβ3 and α5β1 integrin ligands. The starting materials of all the compounds here synthesized are alkylideneacetoacetates. Alkylidene derivates are very usefull compounds, they are usually used as unsaturated electrophiles and they have the advantage of introducing different kind of functionality that may be further elaborated.
In chapter 1, regio- and stereoselective allylic amination of pure carbonates is presented. The reaction proceeds via uncatalyzed or palladium-catalyzed conditions and affords enantiopure dehydro-β-amino esters that are useful precursor of biologically active compounds. Chapter 2 illustrates the synthesis of substituted isoxazolidines and isoxazolines via Michael addition followed by intramolecular hemiketalisation. The investigation on the effect of the Lewis acid catalysis on the regioselectivity of the addition it also reported. Isoxazolidines and isoxazolines are interesting heterocyclic compounds that may be regarded as unusual constrained -amino acids or as furanose mimetics. The synthesis of unusual cyclic amino acids precursors, that may be envisaged as proline analogues, as scaffolds for the design of bioactive peptidomimetics is presented in chapter 3. The synthesis of 2-substituted-3,4-dehydropyrrole derivatives starting from allylic carbonates via a two step allylic amination/ring closing metathesis (RCM) protocol is carried out. The reaction was optimized by testing different Grubbs’ catalysts and carbamate nitrogen protecting groups. Moreover, in view of a future application of these dehydro-β-amino acids as central core of peptidomimetics , the malonate chain was also used to protect nitrogen prior to RCM. Finally, chapter 4 presents the synthesis of two novel different classes of integrin antagonists, one derived from dehydro-β-amino acid prepared as described in chapter 1 and the other one has isoxazolidines synthesized in chapter 2 as rigid constrained core. Since that these compounds are promising RGD mimetics for αvβ3 and α5β1 integrins, they have been submitted to biological assay. and to interpret on a molecular basis their different affinities for the αvβ3 receptor, docking studies were performed using Glide program.
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D’Aurizio, Antonio <1978>. "Microwave-Mediated Hetero Diels-Alder reaction: Synthesis of biologically active compounds." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1641/.
Full textAbstract:
Heterocyclic compounds represent almost two-thirds of all the known organic compounds: they are widely distributed in nature and play a key role in a huge number of biologically important molecules including some of the most significant for human beings.
A powerful tool for the synthesis of such compounds is the hetero Diels-Alder reaction (HDA), that involve a [4+2] cycloaddition reaction between heterodienes and suitable dienophiles.
Among heterodienes to be used in such six-membered heterocyclic construction strategy, 3-trialkylsilyloxy-2-aza-1,3-dienes (Fig 1) has been demonstrated particularly attractive.
In this thesis work, HDA reactions between 2-azadienes and carbonylic and/or olefinic dienophiles, are described.
Moreover, substitution of conventional heating by the corresponding dielectric heating as been explored in the frame of Microwave-Assisted-Organic-Synthesis (MAOS) which constitutes an up-to-grade research field of great interest both from an academic and industrial point of view.
Reaction of the azadiene 1 (Fig 1) will be described using as dienophiles carbonyl compounds as aldehyde and ketones. The six-membered adducts thus obtained (Scheme 1) have been elaborated to biologically active compounds like 1,3-aminols which constitutes the scaffold for a wide range of drugs (Prozac®, Duloxetine, Venlafaxine) with large applications in the treatment of severe diseases of nervous central system (NCS).
Scheme 1
The reaction provides the formation of three new stereogenic centres (C-2; C-5; C-6). The diastereoselective outcome of these reactions has been deeply investigated by the use of various combination of achiral and chiral azadienes and aliphatic, aromatic or heteroaromatic aldehydes.
The same approach, basically, has been used in the synthesis of piperidin-2-one scaffold substituting the carbonyl dienophile with an electron poor olefin.
Scheme 2
As a matter of fact, this scaffold is present in a very large number of natural substances and, more interesting, is a required scaffold for an huge variety of biologically active compounds.
Activated olefins bearing one or two sulfone groups, were choose as dienophiles both for the intrinsic characteristic flexibility of the “sulfone group” which may be easily removed or elaborated to more complex decorations of the heterocyclic ring, and for the electron poor property of this dienophiles which makes the resulting HDA reaction of the type “normal electron demand”.
Synthesis of natural compounds like racemic (±)-Anabasine (alkaloid of Tobacco’s leaves) and (R)- and (S)-Conhydrine (alkaloid of Conium Maculatum’s seeds and leaves) and its congeners, are described (Fig 2).
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Zembower, David Ewing. "The synthesis and structure-activity relationships of biologically active anthraquinones." Diss., Georgia Institute of Technology, 1990. http://hdl.handle.net/1853/26250.
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彭向榮 and Heung-wing Pang. "Studies toward the total synthesis of biologically active cyclodepsipeptides." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31227752.
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Thompson, Leonor. "Enrichment of biologically active compounds from selected plants using adsorptive bubble separation." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973066016.
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Dawson, G. W. "Chemistry of biologically active compounds especially for pest control on arable farms." Thesis, University of Greenwich, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233375.
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Hong, Seoung-Soo. "Synthesis and biological results of compounds acting on alpha- adrenergic receptors /." The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487758680161452.
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Abás, Prades Sònia. "Isocyanide as a key functional group for the synthesis of biologically active compounds." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/586039.
Full textAbstract:
The distinctive reactivity of isocyanides has been recognised as an advantageous characteristic for the formation of heterocyclic compounds. In the present manuscript new synthetic possibilities are explored involving the isocyanide group as the key point for the development of new reactions that allow the access to unpublished compounds. In particular, some of them show very promising pharmacological properties.
According to the different final products accessed, the pharmacological studies and the resulting publications, this dissertation has been classified into six sections.
Synthesis of DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepines (PBDs).
In all the synthesis of C2-endo-unsaturated PDBs published so far, the C2-endo double bond is installed either when the pre-PDB synthon is already synthesized or when the tricyclic core is already built. Both approaches involve several synthetic steps that, unfortunately, in the most part of the examples constitute a considerable drawback.
In order to avoid the cumbersome installation of the double bond after the formation of the tricyclic core, we investigate a new synthetic strategy that relies on the unprecedented use of enantiopure 3-acyl-5-alcoxycarbonyl-2-pyrrolines, synthesized by our group, as key starting materials. Interestingly, the methylketone appendage at the 3-position and the ester substituent at the 5 position are the most suitable to give access to the PBD compounds through known organic transformations.
In this section, objectives, discussion and experimental details to access enantiomerically pure PBDs will be commented.
First diastereoselective [3+2]cycloaddition reaction of diethyl isocyanomethylphosphonate and maleimides published in Org. Biomol. Chem. 2013, 11, 1640-1649.
Bicyclic α-iminophosphonates were prepared via the first diastereoselective silver catalyzed [3 + 2] cycloaddition reaction of diethyl isocyanomethylphosphonate and diversely N-substituted maleimides. The reduction of the resulting imine by catalytic hydrogenation led to cyclic α-aminophosphonates, which are α-aminoester surrogates. The relative stereochemistry of the adducts was confirmed by X-ray crystallographic analysis of one of the compounds. The diastereoselectivity of the cycloaddition reaction was rationalised by theoretical studies.
Easy Access to (2-imidazolin-4-yl)phosphonates by a microwave assisted multicomponent reaction, published in Tetrahedron, 2015, 71, 2872-2881.
An efficient and user-friendly synthetic process involving the combination of multicomponent reaction methodology and microwave heating generates unprecedented (2-imidazolin-4-yl)phosphonates. This strategy presents a silver-catalysed, operationally simple and environmentally friendly transformation without the need of anhydrous atmosphere or additional solvents.
Neuroprotective effects of a structurally new family of high affinity imidazoline I2 receptor ligands published in ACS Chem. Neurosci. 2017, 8, 737-742.
The imidazoline I2 receptors (I2-IRs) are widely distributed in the brain, and I2-IR ligands may have therapeutic potential as neuroprotective agents. Since structural data for I2-IR remains unknown, the discovery of selective I2-IR ligands devoid of α2-adrenoceptor (α2-AR) affinity is likely to provide valuable tools in defining the pharmacological characterization of these receptors. We report the pharmacological characterization of a new family of (2-imidazolin-4-yl)phosphonates. Radioligand binding studies showed that they displayed a higher affinity for I2-IRs than idazoxan, and high I2/α2 selectivity. In vivo studies in mice showed that acute treatments with two of the compounds significantly increased p-FADD/FADD ratio (an index of cell survival) in the hippocampus when compared with vehicle-treated controls. Additionally, acute and repeated treatments with one compound markedly reduced hippocampal p35 cleavage into neurotoxic p25. The present results indicate a neuroprotective potential of (2-imidazolin-4-yl)phosphonates acting at I2-IRs.
Novel compounds as high affinity ligands under revision for protection as a patent and potent transference of technology.La peculiar reactivitat dels isocianoacetats ha estat reconeguda com una avantatjosa característica en la formació de compostos heterocíclics. En aquest manuscrit es presenten noves possibilitat sintètiques utilitzant isocianoacetats com a punt clau per desenvolupar noves reaccions per accedir a nous compostos amb interès farmacològic. L’accés a aquests nous compostos s’ha realitzat a través de dues reaccions principals; les reaccions de cicloaddició i les reaccions multicomponent. En les reaccions de cicloaddició s’ha descrit la preparació de les pirrolbenzodiazepines (PBD), gràcies a la utilització d’un precursor obtingut a través d’una cicloaddició formal [3+2], sota catàlisis cooperativa d’alcaloides de cincona i sals de plata i amb posterior enriquiment de l’excés enantiomèric per self-disproportonation of enantiomers via sublimació. També s’ha descrit la cicloadició [3+2] entre el isocianometilfosfonat de dietil (PhosMic) i maleimides per donar lloc a α-aminofosfonats bicíclics de manera diastereoselectiva, amb la confirmació de la seva estructura relativa per anàlisi de raig X. Pel que fa a les reaccions multimponent s’ha estudiat la reacció entre PhosMic, amines i cetones per donar lloc a les (2-imidazolin-4-il)fosfonats en condicions respectuoses amb el medi ambient, ja que la reacció presenta una elevada economia del àtom, és eficient i transcorre en unes condicions suaus gracies al us del microones. Finalment, la caracterització farmacològica d’aquest compostos en front dels receptor d’imidazolina del tipus 2 (I2-IRs), receptors àmpliament distribuïts en el cervell i relacionats amb activitat neuroprotectora, ha proporcionat nomes eines per poder estudiar-los.
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Verdiá, Báguena Carmen. "Regulation and characterization of membrane protein channels and translocation of biologically active compounds." Doctoral thesis, Universitat Jaume I, 2015. http://hdl.handle.net/10803/667450.
Full textAbstract:
El principal objetivo de la presente Tesis es caracterizar la actividad de
transporte de diferentes canales iónicos, así como regular dicha actividad de
transporte. Por otro lado la Tesis abarca el estudio del transporte a través de
bicapas de moléculas con alto potencial biológico. En este sentido la presente
Tesis abarca diferentes sistemas de estudio que comparten la capacidad de
interactuar con las membranas lipídicas dando como resultado el transporte
iónico a través de la formación de poros, o bien por medio de la translocación a
través de la propia membrana.
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Mostafa, Mohamed A. B. "One-pot transition metal-catalysed processes for the synthesis of biologically active compounds." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/8779/.
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The first section of this thesis describes the development of a one-pot Pd(II)- catalysed Overman rearrangement, Ru(II)-catalysed ring closing enyne metathesis reaction and a hydrogen bond-directed Diels-Alder reaction for the diastereoselective synthesis of C-5 substituted aminobicyclo[4.3.0]nonanes in good yields. To explore the late stage diversification of these compounds, further work investigated a one-pot synthesis of a benzyldimethylsilyl-derived analogue. The synthetic utility of this compound was demonstrated using C–C bond coupling reactions, for the late stage synthesis of a range of sp3-rich bicyclononane scaffolds with up to six stereogenic centres. The second section of this thesis describes the development of a one-pot two-step procedure for aryl C–H amination using iron and copper catalysis. Firstly, a mild and highly regioselective method for the bromination (and chlorination) of arenes via iron(III) triflimide activation of N-bromosuccinimide (or N-chlorosuccinimide) was developed. The scope of both processes was explored for the synthesis of a wide range of aromatic compounds and natural products. The one-pot iron(III)- catalysed bromination/Cu(I)-catalysed N-arylation was then studied. After optimisation, the one-pot two-step process allowed the synthesis of a large library of para-aminated aryl compounds in high yields as single regioisomers.
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Chugtai, Mubashar Ahmed. "An investigation of the generation of some volatile metalloid compounds by biological action." Thesis, Royal Holloway, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326145.
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McCombs, John D. "Studies in marine natural products : Biologically active compounds from the New Zealand algae and invertebrata." Thesis, University of Canterbury. Chemistry, 1989. http://hdl.handle.net/10092/7319.
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In the search for new classes of compounds with antiviral, antitumour or antibacterial activity, a number of benthic marine species were examined.
The extract of Tedania connectens was found to contain three compounds with intense in vitro antiviral and cytotoxic activity (IC₅₀ against P388 murine leukemia cells was 20-40 pg/ml). Examination of the mass spectra of these compounds indicated the presence the known compound tedanolide, together with a deoxy and a chlorinated derivative.
Attempts to convert the antiviral and cytotoxic compound thyrsiferol to thyrsifer-18-one and to the 18-epimer were unsuccessful. However, the ¹H and ¹³C
NMR spectra of thyrsiferyl acetate, including all the pro-r and pro-s proton resonances, were completely assigned using a combination of 2D NMR spectroscopy and molecular mechanics calculations.
Two new dimeric butenolides were isolated from the red alga Delisea elegans, and their structures determined by single X-ray crystallography. The crystal structure of discorhabdin C, a cytotoxic pigment from a sponge of the genus Latrunculia, was determined, as was the crystal structure of the p-bromobenzoyl derivative of the known compound eudistomin K.
Several computer programs were written to assist data analysis. The program
''MassCalc'' was written to free the chemist from the tedious computational tasks usually associated with interpreting mass spectra. A group of five programs were written to simplify the interpretation of the results of molecular mechanics and X-ray crystallography calculations.
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Jamieson, Conor E. "Studies on the mode of action and beta-lactamase inhibitory properties of novel oxapenem compounds." Thesis, Aston University, 2002. http://publications.aston.ac.uk/10943/.
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Four novel oxapenem compounds were evaluated for their -lactamase inhibitory and antibacterial properties. Two (AM-112 and AM-113) displayed intrinsic antibacterial activity with MICs of between 2 to 16 g/ml and 0.5-2g/ml against Escherichia coli and methicillin-sensitive and -resistant Staphylococcus aureus, respectively. The isomers of these compounds, AM-115 and AM-114 did not display significant antibacterial activity. Combination of the oxapenems with ceftazidime afforded protection against -lactamase-producing strains, including hyperproducers of class C enzymes and extended-spectrum -lactamase enzymes. A fixed 4g/ml concentration of AM-112 protected a panel of eight cephalosporins against hydrolysis by class A and class C -lactamase producers. In vivo studies confirmed the protective effect of AM-112 for ceftazidime against -lactamase producing S. aureus, Enterobacter cloacae and E. coli strains in a murine intraperitoneal infection model. Each of the oxapenems inhibited class A, class C and class D -lactamases isolated from whole cells and purified by isoelectric focusing. AM-114 and AM-115 were as effective as clavulanic acid against class A enzymes. AM-112 and AM-113 were less potent against these enzymes. Class C and class D enzymes proved very susceptible to inhibition by the oxapenems. Molecular modelling of the oxapenems in the active site of the class A. TEM-1 and class C P99 enzymes identified a number of potential sites of interaction. The modelling suggested that Ser-130 in TEM-1 and Tyr-150 in P99 were likely candidates for cross-linking of the inhibitor, leading to inhibition of the enzyme. Morphology studies indicated that sub-inhibitory concentrations of the oxapenems caused the formation of round-shaped cells in E. coli DC0, indicating inhibition of penicillin-binding protein 2 (PBP2). The PBP affinity profile of AM-112 was examined in isolated cell membranes of E. coli DC0, S. aureus NCTC 6571, Enterococcus faecalis SFZ and E. faecalis ATCC 29213, in competition with a radiolabelled penicillin. PBP2 was identified as the primary target for AM-112 in E. coli DC0. Studies on S. aureus NCTC 6571 failed to identify a binding target. AM-112 bound to all the PBPs of both E. faecalis strains, and a concentration of 10g/ml inhibited all the PBPs except PBP3.
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Łomzik, Michał Pawel. "Synthesis and characterization of hybrid drugs based on ruthenium complex moiety and biologically active organic compounds." Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0338/document.
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L’objectif de cette thèse est de préparer et caractériser de nouveaux agents théranostiques potentiels à base de complexes de ruthénium portant des molécules biologiquement actives. Pour évaluer potentiel théranostique des nouveaux composés les propriétés de luminescence et la cytotoxicité ont été considérées. Quatre nouveaux ligands portant des substituants a activité biologique: 5-(4-4’-methyl-[2,2’-bipyridine]-4-ylbut-1-yn-1-yl)pyridine-2-carbaldehyde semicarbazone (L1), 3-(5-4’-methyl-[2,2’-bipyridine]-4-ylpentyl)imidazolidine-2,4-dione (L2), 5,5-dimethyl-3-(5-4’-methyl-[2,2’-bipyridine]-4-ylpentyl)imidazolidine-2,4-dione (L3) and [1-(5-4’-methyl-[2,2’-bipyridine]-4-ylpentyl)-2,5-dioxoimidazolidin-4-yl]urea (L4) ont été prepares, caractérisés et engagés dans la synthese des complexes de ruthénium correspondants. Six complexes ont été obtenus a partir du ligand L1 ([Ru(bpy)2(L1)]2+, [Ru(Mebpy)2(L1)]2+, [Ru(tBubpy)2(L1)]2+, [Ru(Phbpy)2(L1)]2+, [Ru(dip)2(L1)]2+, [Ru(SO3dip)2(L1)]2-) et trios a partir de L2, L3 and L4 ([Ru(bpy)2(L2)]2+, [Ru(bpy)2(L3)]2+, [Ru(bpy)2(L4)]2+) (bpy = 2,2’-bipyridine, Mebpy = 4,4’-dimethyl-2,2-bipyridine, tBubpy = 4,4’-tert-butyl-2,2’-bipyridine, Phbpy = 4,4’-diphenyl-2,2-bipyridine, dip = 4,7-diphenyl-1,10-phenantroline and SO3dip = 4,7-di-(4-sulfonatophenyl)-1,10-phenantroline). Les propriétés spectroscopiques et photophysiques des composés ont été étudiées. La présence des ligands L1-L4 conduit a une décroissance du rendement quantique et de la durée de vie de l’état excité en comparaison des complexes non substitués [Ru(bpy)3]2+. Des calculs DFT montrent que les ligands L1-L4 n’influencent pas la géométrie du complexe mais accroissent le niveau énergétique de la HOMO induisant des band gap HOMO-LUMO plus faibles. Les interactions entre les complexes et l’human serum albumin (HSA) ont été étudiées. Tous les complexes préparaés montrent une tres forte affinité pour HSA – La constante d’association 105 M-1s-1 témoigne de la formation d’adduits Ru-HSA stables. Il a aussi été démontré que les complexes de ruthénium se lient préférentiellement a la poche hydrophobe des protéine, située dans le site 1 de Sudlow dans le sous domaine II A. Des études préliminaires ont montré que les complexes de ruthénium préparés presentent une activité cytotoxique vis-à-vis de diverses lignées de cellules cancéreuses. Cette activité associée aux bonnes propriétés de luminescence (rendement quantique, durée de vie) fait des nouveaux complexes des candidats potentiels pour les applications théranostiquesThe main goal of this thesis was synthesis and preliminary characterization of novel ruthenium(II) polypyridyl complexes bearing biologically active molecules as potential theranostic agents. Luminescence for the diagnostic applications, and cytotoxicity for the anticancer, therapeutic applications are considered as the theranostic properties. Four new ligands containing biologically active moieties - 5-(4-4’-methyl-[2,2’-bipyridine]-4-ylbut-1-yn-1-yl)pyridine-2-carbaldehyde semicarbazone (L1), 3-(5-4’-methyl-[2,2’-bipyridine]-4-ylpentyl)imidazolidine-2,4-dione (L2), 5,5-dimethyl-3-(5-4’-methyl-[2,2’-bipyridine]-4-ylpentyl)imidazolidine-2,4-dione (L3) and [1-(5-4’-methyl-[2,2’-bipyridine]-4-ylpentyl)-2,5-dioxoimidazolidin-4-yl]urea (L4) were synthesized and characterized. The ligands were used to obtain nine novel ruthenium(II) polypyridyl complexes. Six complexes were synthesized with ligand L1 ([Ru(bpy)2(L1)]2+, [Ru(Mebpy)2(L1)]2+, [Ru(tBubpy)2(L1)]2+, [Ru(Phbpy)2(L1)]2+, [Ru(dip)2(L1)]2+, [Ru(SO3dip)2(L1)]2-) and three with ligands L2, L3 and L4 ([Ru(bpy)2(L2)]2+, [Ru(bpy)2(L3)]2+, [Ru(bpy)2(L4)]2+) (bpy = 2,2’-bipyridine, Mebpy = 4,4’-dimethyl-2,2-bipyridine, tBubpy = 4,4’-tert-butyl-2,2’-bipyridine, Phbpy = 4,4’-diphenyl-2,2-bipyridine, dip = 4,7-diphenyl-1,10-phenantroline and SO3dip = 4,7-di-(4-sulfonatophenyl)-1,10-phenantroline). The spectroscopic and photophysical properties of those complexes were determined. The presence of ligands L1-L4 in the structure of the complex decreased luminescence quantum yield and luminescence lifetime in comparison with unmodified [Ru(bpy)3]2+ complex. The theoretical calculations have shown that ligands L1-L4 do not have influence on ruthenium core geometry. However, they increased the energy of the HOMO that resulted in a shorter band gap. The simulated electronic absorption spectra were in a good agreement with the experimental data. The interactions between the studied ruthenium complexes and human serum albumin (HSA) were investigated. All studied Ru(II) complexes exhibited strong affinity to HSA with the association constant 105 M-1s-1, which suggests formation of Ru complex-HSA adducts. It was also determined that ruthenium complexes most likely bind to the hydrophobic pocket of protein, located in Sudlow’s site I in the subdomain II A. Preliminary cytotoxicity evaluation for the studied ruthenium complexes showed their cytotoxic activity towards cancer cell lines. Those results, together with good luminescence properties of the studied ruthenium complexes (luminescence lifetimes and luminescence quantum yield) make them interesting candidates for potential theranostic applications
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Mukiza, Janvier. "Synthesis and characterisation of oxorhenium(V) and tricarbonylrhenium(I) complexes with biologically active N, O and N, S-Donor ligands." Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1020769.
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This study investigated the synthesis of rhenium(I) and rhenium(V) complexes with a variety of multidentate NS, NSO, NO and SO-donor ligands. It also investigated the synthesis of dinuclear dihalogeno- and trihalogeno-bridged rhenium(I) complexes based on the fac-[Re(CO)3]+ core. The reactions of hydrated folic acid with [Re(CO)5X] (X = Cl, Br) were studied, and the complexes [Re(CO)3(H2O)3]+[Re2(μ-X)3CO)6]−.5H2O [X= Br (1), Cl(2)] were isolated. The reaction of orotic acid potassium salt [Re(CO)5Br] was performed, and the complex [Re2(μ-Br)2(CO)8] was isolated. The reaction of bis(piperidin-1- yl)methanone with [Re(CO)5Cl] followed by recrystallisation of the resulting precipitate in dichloromethane/acetontrile resulted in the complex [Re2(μ- Cl)2(CO)6(MeCN)2]. The X-ray crystal structures show that all these complexes display a distorted octahedral geometry around the central rhenium atoms. The reactions of aroylhydrazone-based ligands such as 3-((pyridin- 2yl)methyleneamino)-2,3-dihydro-2-pyridin-2yl)quinazolin-4-(1H)-one (Hppq) and N-(di(pyridin-2-yl)methylene)benzohydrazide (Hdpmb) with [Re(CO)5Cl] were studied and led to the formation of the complexes [Re(CO)3Cl(Hdpmb)] and [Re(CO)3Cl(Hppq)]. The Hdpmb and Hppq coordinated to the fac-[Re(CO)3]+ core as neutral bidentate chalates via the pyridinic nitrogens (for Hdpmb) and via imino and pyridinic nitrogens for Hppq. The X-ray crystal structures show that the geometry around the rhenium in both complexes is a distorted octahedral. The treatment of the dithizone (H2dz) ligand with rhenium(V) precursors containing a triphenylphosphine group (PPh3) led to the decomposition of dithizone. The decomposition product reacted with the triphenylphosphine group and generated a new ligand triphenylphosphazeno-N-phenylmethanethiohydrazide (H2L). The reaction of trans-[ReOX3(PPh3)2] (X = Cl, Br) with dithizone (H2dz) led to the complex [ReO(dz)2][ReO(HL)2]. The reaction of trans-[ReOI2(OEt)(PPh3)2] with H2dz led to the same product. The reaction of cis-[ReO2I(PPh3)2] with H2dz in methanol led to [ReO(dz)2][ReO(HL)2](MeOH)2 in which methanol bonded to HLvia hydrogen bonds. The H2dz was doubly deprotonated and coordinated to the [ReO]3+ moiety via a thiolate sulfur and deprotonated hydrazinic nitrogen to yield [ReO(dz)2]−, while the H2L was singly deprotonated and coordinated to [ReO]3+ moiety via the neutral sulfur atom and deprotonated hydrazinic nitrogen to yield [ReO(HL)2]+. The X-ray crystal structure show that in both [ReO(HL)2]+ and [ReO(dz)2]−, the rhenium atoms are five-coordinated and adopt a distorted squarebased pyramidal geometry. The reaction of thiosemicarbazones such as salcylidene-4- phenylthiosemicarbazide (H3salpt) with cis-[ReO2I(PPh3)2] was investigated and led to the complex [ReO(Hsalpt)(H2salpt)]. The X-ray study reveals that Hsalpt is present as a tridentate chelate coordinating via the thiolate sulfur, imino nitrogen and phenolic oxygen, while H2salpt coordinates as a bidentate chelate via the thiolate sulfur and imino nitrogen atoms. The geometry around rhenium is distorted octahedral. The coordination mode of the benzoylthiourea derivatives 4-tert-butyl-N- (diphenylcarbamothioyl)benzamide (Htpb) and N-(diethylcarbamothioyl)benzamide (Heb) to the [Re2O3]4+ and fac-[Re(CO)3]+ cores were investigated. The reaction of [Re(CO)5Cl] in presence of sodium acetate with Htpb led to the dimeric complex [Re(CO)3(tpb)]2 in which the tpb coordinated to the fac-[Re(CO)3]+ core via the ketonic oxygen and bridging thiolate sulfur. The same reaction with Heb led to the monomeric complex [Re(CO)3(eb)(Heb)], in which the eb coordinates to the fac-[Re(CO)3]+core via thiolate sulfur and ketonic oxygen with Heb binding via the neutral sulfur atom. The reaction of Heb with cis-[ReO2I(PPh3)2] at room temperature with excess of sodium acetate led to the dimeric complex (μ-O)[ReO(eb)2]2 in which Heb is present as a monoanionic (deprotonated) bidentate with coordination through the thiolate sulfur and ketonic oxygen.
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López, Antón Nancy. "Identification of novel mechanisms of action contributing to the biological activity of cytotoxic natural compounds." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-53326.
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Mierna, Jana. "Studium biologicky aktivních látek fenyklu." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2018. http://www.nusl.cz/ntk/nusl-376821.
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The master´s thesis is focused on the study of biologically active compounds of fennel. The theoretical part describes basic characteristics of fennel and its chemical composition, further specifies plant´s biological active substances and antioxidants, also describes extraction techniques for obtaining these bioactive compounds, methods of their determination and verification of antimicrobial effect. In the experimental part were spectrophotometrically determined contents of polyphenols and flavonoids in the prepared extracts of fennel tea, whole and crush spice. On the basis of extraction curves, antioxidant activity and potential antimicrobial activity against the selected microorganisms Bacillus subtilis, Bacillus cereus, Serratia marcescens a Micrococcus luteus was determined in the samples with the highest values of the given bioactive substances. Among the all monitored extracts, the inhibitory effect was showed only by an aqueous extract of the fennel tea against the bacterial strain of Micrococcus luteus.
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Humphris, Sonia Naomi. "An investigation of the production of volatile organic compounds (VOCs) by Trichoderma spp. and their mode of action against Serpula lacrymans." Thesis, Abertay University, 2003. https://rke.abertay.ac.uk/en/studentTheses/4e7ad53c-a983-4070-9625-ae8512f67511.
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All living organisms produce volatile compounds that can have a significant effect on the ecological balance within their community. In wood, volatile compounds can build up and become toxic to other resident microorganisms. The major aim of this study was to evaluate the production of volatile compounds by Trichoderma species and evaluate their importance as a mechanism of control of Serpula lacrymans. Volatile interactions between a range of Trichoderma isolates grown on 3 different media (malt extract, minimal media and sawdust) and 4 S. lacrymans isolates demonstrated that levels of inhibition were influenced by Trichoderma isolate, media type and sensitivity of the S. lacrymans strain. The growth inhibition of S. lacrymans consistently resulted in the production of yellow pigmentation in the Serpula mycelium. The greatest levels of inhibition were seen when the Trichoderma were grown on the malt extract media. However, significant levels of inhibition were still recorded when the Trichoderma spp. were grown on a minimal medium (with a carbonmitrogen ratio similar to that found in Scots pine sawdust) and sawdust. The growth inhibition of S. lacrymans on the minimal media and sawdust is likely to provide a much more realistic guide to levels of inhibition that might be expected in the field. Gas chromatograph-mass spectrometry and associated principal component analysis of the Trichoderma VOCs resulted in the identification of 8 volatile compounds, mainly ketones, which were implicated as the active VOCs involved in the inhibition of S. lacrymans. The range and quantity of volatiles produced was dependent on the Trichoderma isolate and the media on which it was growing. If Trichoderma. is to be successful as a remedial treatment of dry rot in buildings, the volatiles identified as active inhibitory compounds must also be produced by the potential biocontrol agent in wood. Therefore, compounds of particular interest were 3-octanone, 2-nonanone and 2-heptanone, as they were produced by the most inhibitory treatment (T. aureoviride when grown on malt extract) but also produced on the sawdust. After exposure of the S. lacrymans strains to the Trichoderma VOCs, the Serpula cultures were assayed for production of 3 enzymes, cellulase, tyrosinase and peroxidase. The results demonstrated that the Trichoderma VOCs did not affect cellulase production. Therefore, while there would be a decrease in cellulase production, due to the reduction in S. lacrymans biomass, caused by the inhibition of growth by the Trichoderma VOCs, S. lacrymans would still be capable of degrading cellulose. Tyrosinase production was not detected in any of the cultures of S. lacrymans. Since yellow pigmentation was detected in plates of S. lacrymans inhibited by the Trichoderma VOCs it is unlikely that tyrosinase plays a role in this pigmentation in Serpula. Increased peroxidase production was detected in all plates of S. lacrymans displaying yellow pigmentation, suggesting that increased peroxidase production is linked to increased pigmentation associated with a stress reaction in S. lacrymans. SDS-PAGE analysis of protein production indicated changes in the protein profiles of S. lacrymans isolates when exposed to inhibitory VOCs from Trichoderma. One protein band in particular, at molecular weight 22.4 kDa, appeared to be closely linked to levels of growth inhibition with production of this protein completely inhibited by the VOCs from T. aureoviride, which gave the greatest levels of inhibition of the S. lacrymans isolates. The protein was unaffected by VOCs from T. pseudokoningii, which gave very little or no inhibition of growth of S. lacrymans, while VOCs from T. viride (which gave on average between 35-50% inhibition of growth) caused a marked reduction in synthesis of this protein. Analysis of this protein by electrospray ionisation did not, however, result in the identification of this protein. Removal of the antagonistic VOC stress demonstrated that the inhibition of S. lacrymans growth was transient, with not only growth resuming but production of all proteins previously inhibited also resuming. This work has shown that VOC production by Trichoderma spp. can have a fundamental role in microbial ecology of ecosystems dominated by fungi and for the first time has shown both up and down regulation of protein production in S. lacrymans after exposure and subsequent removal of inhibitory Trichoderma VOCs.
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Calder, Ewen D. D. "The development of one-pot multi-reaction processes for the synthesis of natural products and biologically active compounds." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6667/.
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This thesis is divided into four chapters in which one-pot processes have been developed and utilised for the synthesis of biologically active compounds. The work in the first chapter outlines the 13-step total synthesis of D -ribo- and L - arabino-phytosphingosine from D -ribose. This process employed a microwave promoted Overman rearrangement of an allylic trichloroacetimidate to install the amine functionality. In the second and third chapters, the development of a one-pot, two-step Overman/ring closing metathesis process is detailed. The synthesis of three different classes of starting material is also shown. This one-pot process was used as the key step in the synthesis of four oxybenzo[c]phenanthridine natural products and the partial synthesis of an ACAT inhibitor. The potential for further functionalisation of the products by oxidation and reduction was also explored. In the final chapter, a one-pot allylboration/Heck process for the synthesis of indan-1-ols is described. Optimisation and an investigation of the scope of the process are also presented. The process was then altered to allow the use of a chiral phosphoric acid catalyst for the asymmetric synthesis of these compounds.
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Bång, Joakim. "Purification, Stereoisomeric Analysis and Quantification of Biologically Active Compounds in Extracts from Pine Sawflies, African Butterflies and Orchid Bees." Doctoral thesis, Mittuniversitetet, Institutionen för naturvetenskap, teknik och matematik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-14662.
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Stereochemistry plays an important role in nature because biologically important molecules such as amino acids, nucleotides and sugars, only exist in enantiomerically pure forms. Semiochemicals carry messages, between the same species (pheromones) and between different species (allelochemicals). Both pheromones and allelochemicals can be used as environmentally friendly pest management. Many semiochemicals, i.e. behaviour modifying chemicals, consist of pure or well-defined mixtures of stereoisomers, where some of the other stereoisomers can be repellent. It is therefore important to be able to separate them to produce a synthetic pheromone in a mixture that is attractive. Pine sawflies are a family of insects that in some cases can be severe defoliators of conifer trees. Diprion pini, Diprion similis and Neodiprion sertifer are severe pests for these trees and have got the most attention in pine sawfly pheromone studies. The pheromone precursors are stored in the female body as long-chain secondary alcohols, which, when released, are esterified to acetates or propionates. The alcohols are chiral, and normally one of the stereoisomer is the main pheromone component, sometimes possible together with other stereoisomers as essential minor components. Bicyclus is a genus of African butterflies, and especially Bicyclus anynana has become a popular model for the study of life history evolution, morphology, mating choice and genetics. The wing pattern of Bicyclus differs depending on the season, with large eyespots during the rain-season and small or absent spots during the dry season. Euglossa is one of the genera among the orchid bees in the Neotropics that does not produce its own pheromone. Instead, the males collect fragrances from orchids and other sources and store them in a pocket in their hind legs. Both Bicyclus and Euglossa use semiochemicals similar to pine sawflies, and thus can be analysed by the same methods. Pheromones and other semiochemicals in insects are often present in low amounts in a complex matrix, and purification of the sample before chemical analysis is often required. A common method is gradient elution on a solid phase silica column. Separation of stereoisomers can be achieved either by using a column with a chiral stationary phase (CSP) or with pre-column derivatisation using a column with an achiral stationary phase (ASP) or a combination of both, with mass detection as the dominant detection method. The purpose of this work has been to improve the purification method, find suitable methods to separate the stereoisomers of secondary alcohols, and to apply this on extracts of insects. By selecting the right fractions to collect during gradient elution the purification method was optimised. To reduce plasticizer contamination from ordinary columns, solid phase columns of Teflon or glass were used. For pre-column derivatisation of different chiral alcohols various acid chlorides were tested. For the pine sawfly pheromone precursors enantiopure (2S)-2-acetoxypropionyl chloride was the best choice. To separate some of the stereoisomers achiral 2-naphthoyl chloride was used. For derivatisation of 6,10,14-trimethylpentadecan-2-ol (R)-trans-chrysanthemoyl chloride was the best choice. The derivatised alcohols were separated on different columns, both chiral and non-chiral. Varian FactorFour VF-23ms was chosen as a general-purpose column, the Agilent HP-88 column was the best column with an ASP of those tested, and the Chiraldex B-PA column (CSP) was the only one that could separate all eight stereoisomers of derivatised 3,7-dimethylundecan-2-ol, 3,7-dimethyldodecan-2-ol, and 3,7-dimethyltridecan-2-ol. To determine the stereoisomeric purity of standard solutions used in field experiments and extracts of different species of insects the optimised methods were applied. For extracts from B. anynana, Euglossa and Neodiprion lecontei this work describe the first determination of the stereochemistry of some of their semiochemicals. For the determination of the stereochemistry of chiral semiochemicals the methods for purification and separation presented herein have shown to be of great value. The results will hopefully contribute to a better understanding of the communication among insects, and ultimately to a more environmentally friendly pest control.Många naturligt förekommande kemiska ämnen finns som två spegelbilder av varandra, ungefär som höger och vänster hand. Dessa kan ha helt olika egenskaper och det är därför viktigt att kunna separera dem. Insekter och andra djur använder olika doftämnen för att kommunicera med varandra, om det är inom samma art kallas de för feromoner. De kan bestå av ett ämne eller en blandning av flera. Dessa doftämnen kan man även använda för att på ett miljövänligt sätt bekämpa skadeinsekter. En fälla med syntetiskt feromon för en viss insekt lockar endast till sig den arten, medan alla andra är opåverkade. Eftersom dessa ämnen ofta finns som spegelbilder där kanske bara den ena är aktiv och den andra rent av frånstötande, måste man kunna separera dem för att framställa ett syntetiskt feromon som är attraktivt. Målet med detta arbete har varit att bestämma feromonet hos olika arter av tallsteklar som kan vara svåra skadedjur på tallskog. De metoder som tagits fram har även tillämpats på några arter av afrikanska fjärilar samt orkidébin från Centralamerika eftersom de använder snarlika doftämnen. Att få fram feromonet från en insekt är lite som att leta efter in nål i en höstack eftersom de ofta bara innehåller några miljarddels gram per individ. Provet behöver först renas, och en del av arbetet i det här projektet har gått ut på att ta fram en lämplig reningsmetod. Huvudfokus har dock varit på att ta fram metoder som kan separera och identifiera det eller de ämnen, och spegelbilder av dessa, som doftämnena består av. När lämpliga metoder tagits fram har extrakt av olika insektsarter analyserats. I några fall är det första gången som deras feromon bestämts i detalj. Resultaten kan förhoppningsvis bidra till en ökad kunskap om insekters sätt att kommunicera, och i slutändan till miljövänligare bekämpning av skadeinsekter.
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Sereda, Oksana Volodymyrivna. "Development of novel Lewis acid and Lewis base organocatalysts and their application in the synthesis of biologically active compounds." Clausthal-Zellerfeld Papierflieger, 2009. http://d-nb.info/997006943/04.
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Jacobsen, Elisabeth Egholm. "Synthesis of enantiopure building blocks for biologically active compounds by enzyme catalysis. Optimizing reaction conditions for increased enantioselectivity and activity." Doctoral thesis, Norwegian University of Science and Technology, Department of Chemistry, 2004. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-2098.
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Efficient methods for synthesis of enantiomerically pure enantiomers of a series of secondary alcohols and butanoates have been performed by kinetic resolution of the racemic alcohols and esters catalyzed by lipase B from Candida antarctica (Novozym 435). The effect of the substrate structure on E was different for transesterifications of alcohols in organic media as compared to hydrolysis of esters in buffer. The influence of different acyl donors on the enantioselectivity has also been investigated.
Derivatives of 1-phenoxy-2-alkanols have been kinetically resolved by esterification with irreversible and reversible acyl donors using lipase B from Candida antarctica (Novozym 435) as catalyst. Esterifications in eight different solvents with different water activity have been performed. For 3-bromo-1-phenoxy-2-propanol the E-values in all of the solvents were higher when the water activity was increased. The water content of the various reaction media at the same water activity was also determined.
In esterifications of secondary alcohols catalyzed by immobilized lipase B from Candida antarctica (Novozym 435) the E-values decreased during the reaction. Hydrolysis of the corresponding butanoates showed the opposite effect. When an enantiopure (R)-alcohol, related but different, was added to the transesterification reaction, the E-value was significantly enhanced.
Decreasing enantioselectivity (E-value) by conversion has also been observed in transesterification reactions of secondary alcohols catalyzed by a pure protein formulation of lipase B from Candida antarctica (Novozym 525 F). It can be concluded that the immobilization of Novozym 435 not was the reason for the decrease in E-value which was observed. Addition of a range of enantiopure alcohols caused a temporary increase in enzyme selectivity in the transesterification reaction of 3-chloro-1-phenoxy- 2-propanol with vinyl butanoate.
Enantioselective hydrolyses and ammonolyses of diethyl 3-hydroxyglutarate and dimethyl 3-hydroxyglutarate gave a maximum of 91 and 98 % enantiomeric excess, respectively, with use of immobilized lipase B from Candida antarctica (Novozym 435). Ee´s were determined using chiral GLC of the mono amides and achiral GLC of diastereomeric derivatives of the monoesters. The catalyst was re-used more than ten times with retention of high activity and selectivity.
Biocatalytic asymmetrizations of diethyl 3-hydroxyglutarate furnish a route to enantiomers of ethyl 4-cyano-3-hydroxybutanoate. The enantiopreference of different enzymes has been established by chiral chromatography. Conclusive evidence for absolute configurations has been provided by X-ray crystallographic structure determination of co-crystals of the predominant monoester (3S)-3-hydroxy pentanedioic monoethyl ester with (R)-phenylethylamine. The predominant enantiopure monoester produced by ammonolysis of diethyl 3-hydroxyglutarate catalyzed by immobilized lipase B from Candida antarctica (Novozym 435) was ethyl (3S)-4-carbamoyl-3- hydroxybutanoate. It was converted to ethyl (3S)-4-cyano-3-hydroxybutanoate in high yield and enantiomeric excess.
Paper III, IV, V, and VI are reproduced with kind permission of Elsevier, sciencedirect.com
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Mosrin, Marc [Verfasser], and Paul [Akademischer Betreuer] Knochel. "Regio- and chemoselective metalations of N-heterocycles : applications to the synthesis of biologically active compounds / Marc Mosrin ; Betreuer: Paul Knochel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/118479412X/34.
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El-Sayed, Mardia El-Dessoky Teleb [Verfasser], Andreas [Akademischer Betreuer] Hilgeroth, Sibel [Akademischer Betreuer] Suzen, and Michael [Akademischer Betreuer] Lalk. "Development of novel indolyl-derived biologically active compounds / Mardia El-Dessoky Teleb El-Sayed. Betreuer: Andreas Hilgeroth ; Sibel Suzen ; Michael Lalk." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2013. http://d-nb.info/1041255640/34.
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Watanabe, Toshiaki. "Synthetic Studies on Nitrogen Heterocycles by Transition Metal-Catalyzed C-H Bond Functionalization and Their Synthetic Application to Biologically Active Compounds." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120510.
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Benedetti, Brad. "Drug Design, Biological Activity, and Metabolic Consequences of Cytotoxic Platinum Compounds: Utilizing Fluorescent Tagging to Understand Drug Action and Metabolism." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/195.
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Platinum drugs are among the most commonly used chemotherapeutics for the treatment of testicular, head and neck, ovarian, small cell lung, and colorectal carcinomas. Although the current set of platinum chemotherapeutics has proven somewhat successful, the overall success of platinum based drugs is limited due to acquired drug resistance and a limited range of tumor types that are treatable with the current regime. The development of novel cytotoxic platinum based compounds, both trans- and polynuclear, provides for the promising treatment of clinical platinum drug resistant tumors. While the cytotoxic activity of platinum drugs provides for a hopeful outlook, the ultimate factors that affect the success of chemotherapeutics are the fine balance between cytotoxic activity and metabolic deactivation. In general, this work reports the drug design/drug action, and pharmacokinetic consequences of anticancer compounds aimed to fight mechanisms of cisplatin resistance. In the first project, we report the biological and biophysical studies aimed at understanding and improving upon the pharmacokinetic properties of chemotherapeutics; specifically, understanding their interactions with serum proteins. This work resulted in the discovery of using carboxylate ligands to modulate the reactivity of trans-platinum based compounds towards sulfur containing proteins with consequent effects on drug efficacy. In addition, we report an in depth look into the biological consequences of non-covalent platinum drug-protein interactions on drug efficacy, and introduce the use of novel Platinum-NBD fluorescent conjugates as probes for drug metabolism. In the second project we report the design, synthesis, and biological consequences of fluorescent drug derivatives based on the NBD fluorophore, for use in understanding drug action and drug metabolism. As a result of this fluorescent drug labeling, TriplatinNC, a non-covalent platinum based chemotherapeutic, was found to specifically target nucleolar DNA/RNA, due to its high charge, and inhibit ribosomal RNA production in cancer cells. The use of fluorescent derivatization also resulted in the development of a series of novel water-soluble trans-platinum complexes, with greater cytotoxicity than cisplatin. Therefore, these data resulted in the understanding of, and improvement upon the pharmacokinetic profile of platinum chemotherapeutics, as well as the development of novel fluorescent platinum conjugates with novel metabolic and cytotoxic profiles.
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El, Achkar Tracy. "Deep eutectic solvents : characterization, interaction with synthetic and biological membranes, and solubilization of bioactive volatile compounds." Thesis, Littoral, 2020. http://www.theses.fr/2020DUNK0562.
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Les solvants eutectiques profonds (DES) sont récemment apparus comme une nouvelle classe de solvants verts présentant un potentiel élevé pour remplacer les solvants organiques usuels. Bien que découverts récemment, les DES ont fait l'objet de nombreuses recherches au cours des dernières années en raison de leurs propriétés intéressantes. Cependant, il reste encore beaucoup à découvrir étant donné le nombre quasiment illimité de DES potentiels et de leur polyvalence. Notre étude vise à examiner l'effet des DES sur les liposomes, adoptés comme modèles membranaires, et sur les membranes cellulaires. Elle a également cherché à évaluer la capacité de solubilisation des DES envers des composés bioactifs volatils. Ainsi, une sélection de DES ainsi que de nouveaux solvants ont été tout d'abord préparés et caractérisés. Des mesures de densité, de viscosité et de polarité ont été effectuées et ont montrées que les propriétés des DES pouvaient être ajustées en fonction de leur composition. L'organisation des phospholipides et des liposomes au sein des DES a ensuite été étudiée à l'aide de microscopies optique et à force atomique. Les phospholipides s'auto-assemblent en vésicules dans les DES à base de chlorure de choline tandis que les liposomes se convertissent en bicouches lipidiques avant leur reconstitution en vésicules. De plus, des études de cytotoxicité et des examens morphologiques ont été combinés afin d'évaluer l'impact de quelques DES sur MDA-MB-231, une lignée cellulaire de cancer du sein humain. Les résultats ont montrés que l'effet dépendait fortement de la composition du DES. D'autre part, la capacité de solubilisation des DES envers des composés bioactifs volatils a été testée par chromatographie en phase gazeuse couplée à un espace de tête. L'influence de la présence d'eau et de certains systèmes d'encapsulation tels que les liposomes et les cyclodextrines sur la capacité de solubilisation des DES ont été analysés. Enfin, la libération du trans-anéthole à partir des DES a été suivie par extraction multiple de l'espace de tête. Les DES ont été capables de mieux solubiliser les composés bioactifs volatils et de contrôler leur libération par rapport à l'eau. Dans l'ensemble, ces travaux mettent en évidence l'utilisation potentielle des systèmes à base de DES comme véhicules de solubilisation de composés bioactifsDeep eutectic solvents (DES) recently emerged as a novel class of green solvents with a high potential to replace common organic solvents. Despite their novelty, DES were extensively explored in the past years owing to their remarkably interesting properties. Yet, a lot remains to be uncovered given the limitless number of possible DES and their versatility. The current sudy aimed to examine the effect of DES on liposomes, adopted as model membranes, and on cell membranes. It also sought to evaluate the solubilizing ability of DES toward bbioactive volatile compounds. Therefore, a group of selected DES along with new solvents were first prepared and characterized. Density, viscosity and polarity measurements were mainly carried out and showed that DES' properties can be tuned depending on their composition. The organization of phospholipids and liposomes within the DES was then investigated using optical- and atomical force microscopies. Phospholipids self-assembled into vesicles in choline chloride-based DES while liposomes converted to lipid bilayers before their reconstitution into vesicles. Moreover, cytotoxicity studies and morphological examinations were combined to evaluate the impact of some DES on MDA-MB-231, a human breast cancer cell line. Results showed that the effect is highly dependent on the DES' composition. On the other hand, the solubilizing ability of the DES toward bioactive volatile compounds was tested using static headspace-gas chromatography. The influence of the presence of water and some encapsulation systems such as liposomes and cyclodextrins on the overall DES' solubilization efficiency was further analyzed. At last, the release of trans-anethole from the DES was monitored via multiple headspace extraction. DES were able to greatly solubilize the bioactive volatile compounds and to control their release when compared with water. Altogether, this work highlights the potential use of the DES-based systems as solubilization vehicles for bioactive compounds