The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform
Michael J Waring - One of the best experts on this subject based on the ideXlab platform.
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tight binding of the antitumor drug ditercalinium to quadruplex dna
ChemBioChem, 2002Co-Authors: Carolina Carrasco, Christiane Garbayjaureguiberry, Bernard P Roques, Frederic Rosu, Valerie Gabelica, Claude Houssier, Edwin De Pauw, David W Wilson, Jonathan B Chaires, Michael J WaringAbstract:The structural selectivity of the DNA-binding antitumor drug ditercalinium was investigated by competition dialysis with a series of nineteen different DNA substrates. The 7H-Pyridocarbazole dimer was found to bind to double-stranded DNA with a preference for GC-rich species but can in addition form stable complexes with triplex and quadruplex structures. The preferential interaction of the drug with four-stranded DNA structures was independently confirmed by electrospray mass spectrometry and a detailed analysis of the binding reaction was performed by surface plasmon resonance (SPR) spectroscopy. The BIAcore SPR study showed that the kinetic parameters for the interaction of ditercalinium with the human telomeric quadruplex sequence are comparable to those measured with a duplex sequence. Slow association and dissociation were observed with both the quadruplex and duplex structures. The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG3[T2AG3]3) provides new perspectives for the design of drugs that can bind to human telomeres.
Carolina Carrasco - One of the best experts on this subject based on the ideXlab platform.
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tight binding of the antitumor drug ditercalinium to quadruplex dna
ChemBioChem, 2002Co-Authors: Carolina Carrasco, Christiane Garbayjaureguiberry, Bernard P Roques, Frederic Rosu, Valerie Gabelica, Claude Houssier, Edwin De Pauw, David W Wilson, Jonathan B Chaires, Michael J WaringAbstract:The structural selectivity of the DNA-binding antitumor drug ditercalinium was investigated by competition dialysis with a series of nineteen different DNA substrates. The 7H-Pyridocarbazole dimer was found to bind to double-stranded DNA with a preference for GC-rich species but can in addition form stable complexes with triplex and quadruplex structures. The preferential interaction of the drug with four-stranded DNA structures was independently confirmed by electrospray mass spectrometry and a detailed analysis of the binding reaction was performed by surface plasmon resonance (SPR) spectroscopy. The BIAcore SPR study showed that the kinetic parameters for the interaction of ditercalinium with the human telomeric quadruplex sequence are comparable to those measured with a duplex sequence. Slow association and dissociation were observed with both the quadruplex and duplex structures. The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG3[T2AG3]3) provides new perspectives for the design of drugs that can bind to human telomeres.
Rosângela De A. Epifanio - One of the best experts on this subject based on the ideXlab platform.
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Two fast screening methods (GC-MS and TLC-ChEI assay) for rapid evaluation of potential anticholinesterasic indole alkaloids in complex mixtures
Anais da Academia Brasileira de Ciencias, 2008Co-Authors: Ivo José Curcino Vieira, Walter L.b. Medeiros, Cecilia Silva Monnerat, Jucimar Jorgeane De Souza, Leda Mathias, Raimundo Braz-filho, Angelo C. Pinto, Priscila Mesquita De Sousa, Claudia M. Rezende, Rosângela De A. EpifanioAbstract:The pharmacotherapyfor Alzheimer's disease (AD) includes the use of acetylcholinesterase inhibitors (AChEI). Recent investigations for novel AD therapeutic agents from plants suggested that Tabernaemontana genus is a promising source of novel anticholinesterasic indole alkaloids. In this work two fast screening techniques were combined in order to easily identify novel cholinesterase inhibitors (ChEI). Gas chromatography-mass spectrometry (GC-MS) of the less polar alkaloidic fractions obtained from the acid-base extraction of the stalk of T. laeta revealed thirteen monoindole alkaloids, four of them confirmed by co-injection with previously isolated alkaloids. The others were tentatively identified by mass fragmentation analysis. By gas chromatography with flame ionization detection (GC-FID) and using isatin as internal standard, affinisine and voachalotine were determined as major compounds. These fractions and fourteen previously isolated alkaloids, obtained from root bark of T. laeta and T. hystrix were investigated for acetyl (AChE) and butyrylcholinesterase (BuChE) inhibitory activities by the modified Ellman's method in thin layer chromatography(TLC-ChEI). Results showed selective inhibition of the alkaloids heyneanine and Nb-methylvoachalotine for BuChE, and 19-epi-isovoacristine for AChE, whereas olivacine, affinisine, ibogamine, affinine, conodurine and hystrixnineinhibited both enzymes. In addition to confirming that monoterpenoid indole alkaloids can be novel therapeutic agents for AD, this is the first report of the ChEI activity of olivacine, a Pyridocarbazole alkaloid.
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Two fast screening methods (GC-MS and TLC-ChEI assay) for rapid evaluation of potential anticholinesterasic indole alkaloids in complex mixtures
Academia Brasileira de Ciências, 2008Co-Authors: Ivo José Curcino Vieira, Walter L.b. Medeiros, Cecilia Silva Monnerat, Jucimar Jorgeane De Souza, Leda Mathias, Raimundo Braz-filho, Angelo C. Pinto, Priscila Mesquita De Sousa, Claudia M. Rezende, Rosângela De A. EpifanioAbstract:The pharmacotherapyfor Alzheimer's disease (AD) includes the use of acetylcholinesterase inhibitors (AChEI). Recent investigations for novel AD therapeutic agents from plants suggested that Tabernaemontana genus is a promising source of novel anticholinesterasic indole alkaloids. In this work two fast screening techniques were combined in order to easily identify novel cholinesterase inhibitors (ChEI). Gas chromatography-mass spectrometry (GC-MS) of the less polar alkaloidic fractions obtained from the acid-base extraction of the stalk of T. laeta revealed thirteen monoindole alkaloids, four of them confirmed by co-injection with previously isolated alkaloids. The others were tentatively identified by mass fragmentation analysis. By gas chromatography with flame ionization detection (GC-FID) and using isatin as internal standard, affinisine and voachalotine were determined as major compounds. These fractions and fourteen previously isolated alkaloids, obtained from root bark of T. laeta and T. hystrix were investigated for acetyl (AChE) and butyrylcholinesterase (BuChE) inhibitory activities by the modified Ellman's method in thin layer chromatography(TLC-ChEI). Results showed selective inhibition of the alkaloids heyneanine and Nb-methylvoachalotine for BuChE, and 19-epi-isovoacristine for AChE, whereas olivacine, affinisine, ibogamine, affinine, conodurine and hystrixnineinhibited both enzymes. In addition to confirming that monoterpenoid indole alkaloids can be novel therapeutic agents for AD, this is the first report of the ChEI activity of olivacine, a Pyridocarbazole alkaloid.Dentre os tratamentos da doença de Alzheimer (DA) está o uso de inibidores da enzima acetilcolinesterase. Pesquisas recentes visando a descoberta de novos agentes terapêuticos naturais para esta doença sugerem que o gênero Tabernaemontana é uma fonte promissora de alcalóides indólicos anticolinesterásicos. Neste trabalho, duas técnicas de análise em mistura foram associadas de modo a identificar facilmente novos inibidores colinesterásicos. A cromatografia em fase gasosa acoplada a espectrometria de massas (CG-EM) das frações alcaloídicas apolares, obtidas da extração ácido-base do caule de T. laeta, revelou a presença de treze alcalóides monoindólicos, quatro deles confirmados por co-injeção com padrões previamente isolados. Os outros alcalóides foram tentativamente identificados pelo padrão de fragmentação de massas. Por cromatografia em fase gasosa com detecção por ionização de chama (CG-DIC) e utilizando isatina como padrão interno, affinisina e voachalotina foram identificadas como substâncias majoritárias. As frações alcaloídicas obtidas e os quatorze alcalóides previamente isolados das raízes de T. laeta e T. hystrix foram analisados quanto à atividade inibitória das enzimas acetil (AChE) e butirilcolinesterase (BuChE) pelo método de Ellman em cromatografia em camada delgada (CCD-ChEI). Os resultados revelaram uma inibição seletiva dos alcalóides heyneanina e Nb-metilvoachalotina para BuChE e de 19-epi-isovoacristina para AChE, enquanto que olivacina, affinisina, ibogamina, affinina, conodurina e hystrixnina inibiram ambas as enzimas. Além de confirmar que alcalóides indólicos monoterpênicos são agentes terapêuticos promissores para o tratamento da DA, este é o primeiro relato da atividade anticolinesterásica de olivacina, um alcalóide piridocarbazólico
Blache Yves - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and Biological Evaluation of Indoloquinolines and Pyridocarbazoles: A New Example of Unexpected Photoreduction Accompanying Photocyclization
'Pharmaceutical Society of Japan', 2007Co-Authors: Aragon Pierre-jean, Yapi Ange-désiré, Pinguet Frédéric, Chezal Jean-michel, Teulade Jean-claude, Blache YvesAbstract:International audienceIndoloquinoline alkaloid cryptolepine and Pyridocarbazole alkaloid ellipticine are of great interest because in vitro and in vivo studies revealed their good cytotoxic properties. In order to obtain some biologically active analogs of these compounds, we developed a synthesis based on the photocyclization of tertiary N-substituted enaminones derived from 1,3-cyclohexandione and 3 or 6-aminoquinoline. The angular cyclized compounds thus obtained were tested in vitro on K 562 cells and A 2780 doxorubicin sensitive and resistant cells. All compounds were less effective than doxorubicin in sensitive cells but their activity wasn’t decreased by MDR resistance
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A Photochemical Approach to Pyridopyrroloquinoline Derivatives as New Potential Anticancer Agents
'Pharmaceutical Society of Japan', 2004Co-Authors: Aragon Pierre-jean, Yapi Ange-désiré, Pinguet Frédéric, Chezal Jean-michel, Teulade Jean-claude, Chapat Jean-pierre, Blache YvesAbstract:International audienceIndoloquinoline alkaloid cryptolepine and Pyridocarbazole alkaloid ellipticine are of great interest becausein vitro and in vivo studies revealed their good cytotoxic properties. In order to obtain some biologically activeanalogs of these compounds, we developped a synthesis based on the photocyclisation of tertiary N-methylatedenaminones derived from cyclopentane-1,3-dione and 3 or 6-aminoquinoline. The angular cyclised compoundsthus obtained were submitted to Beckmann rearrangement, preceded by the formation of a Z oxime. Finally, thed -lactame ring was oxidized using 10% palladium/carbon in diphenylether and pyridopyrroloquinolines wereobtained. These compounds and the intermediate lactams and cyclopentanopyrroloquinolines were tested in vitroon K 562 cells and A 2780 doxorubicine sensitive and resistant cells. All compounds were less effective than doxorubicine in sensitive cells but their activity wasn’t decreased by MDR resistance
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Synthèse et évaluation de la cytotoxicité de carbolines, indoloquinolines et Pyridocarbazoles à potentialité anticancéreuse
2003Co-Authors: Aragon Pierre-jean, Blache YvesAbstract:En progression constante, le cancer est un défi médical majeur. Au vu de la potentialité anticancéreuse des composés polycicliques azotés comme la cryptolépine, l'ellipticine,la murrayaquinone A et l'amarorine, la synthèse par voie photochimique d'analogues de ces substances a été envisagée. Les squelettes carboline, indoloquinoléine, et Pyridocarbazole sont obtenus en deux ou trois étapes à partir d'énaminones issues d'aminopyridines ou d'aminoquinoléines et de cyclohexanedione : synthèse de l'énaminone, éventuelle N-alkylation, photocyclisation. Le squelette pyridopyrroloquinoléine est obtenu à partir d'aminoquinoléine et de cyclopentanedione, par une synthèse incluant deux étapes clés : une photocyclisation et une transposition de Beckmann. Les tests de cytotoxicité in vitro des dérivés d'aminoquinoléines ont révélé les composés les plus actifs, les premières relations structure-activité et l'absence de sensibilité de ces composés à la résistance MDR.MONTPELLIER-BU Pharmacie (341722105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Frederic Rosu - One of the best experts on this subject based on the ideXlab platform.
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tight binding of the antitumor drug ditercalinium to quadruplex dna
ChemBioChem, 2002Co-Authors: Carolina Carrasco, Christiane Garbayjaureguiberry, Bernard P Roques, Frederic Rosu, Valerie Gabelica, Claude Houssier, Edwin De Pauw, David W Wilson, Jonathan B Chaires, Michael J WaringAbstract:The structural selectivity of the DNA-binding antitumor drug ditercalinium was investigated by competition dialysis with a series of nineteen different DNA substrates. The 7H-Pyridocarbazole dimer was found to bind to double-stranded DNA with a preference for GC-rich species but can in addition form stable complexes with triplex and quadruplex structures. The preferential interaction of the drug with four-stranded DNA structures was independently confirmed by electrospray mass spectrometry and a detailed analysis of the binding reaction was performed by surface plasmon resonance (SPR) spectroscopy. The BIAcore SPR study showed that the kinetic parameters for the interaction of ditercalinium with the human telomeric quadruplex sequence are comparable to those measured with a duplex sequence. Slow association and dissociation were observed with both the quadruplex and duplex structures. The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG3[T2AG3]3) provides new perspectives for the design of drugs that can bind to human telomeres.
