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Ferrando Ruana Francesc - One of the best experts on this subject based on the ideXlab platform.
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Reaccions intramolecualrs de radicals 2-indolilacil: aplicació a la síntesi de compostos indòlics
'Edicions de la Universitat de Barcelona', 2006Co-Authors: Ferrando Ruana FrancescAbstract:[cat] La present Tesi Doctoral es situa en el context de les reaccions intramoleculars de radicals 2-indolilacil i està constituïda, d'acord amb els objectius inicials, per dues parts. La primera part centra l'atenció en les ciclacions de radicals 2-indolilacil en condicions reductores, emprant alquens com a acceptors radicalaris per a l'obtenció d'estructures que formen part de productes naturals i d'altres compostos bioactius. En aquest context s'ha aconseguit: - El desenvolupament d'un nou procediment d'anulació indòlica que permet accedir a cetones cícliques 1,2-fusionades amb l'indole. - La síntesi total de l'alcaloide (±)-guatambuïna i la síntesi formal de l'alcaloide olivacina. La segona part es situa en el context de les reaccions intramoleculars de radicals 2-indolilacil amb sistemes aromàtics. Els principals aconseguiments en aquesta part són: - La ciclació de radicals 2-indolilacil sobre anells de benzè en condicions no reductores (n-Bu6Sn2-hvper donar de manera eficient indolil fenil cetones tetracícliques. - La ciclació regioselectiva de radicals 2-indolilacil sobre piridines en condicions no reductores (n-Bu6Sn2-hv per donar indolil 4-piridil cetones tetracícliques. L'efectivitat d'aquest protocol radicalari permet el fàcil accés a elipticina quinones. - La ciclació de radicals 3-(3-quinolil)metil-2-indolilacil en condicions reductores (TTMSS-AIBN) per donar pentacicles relacionats amb la calotrixina, l'estat d'oxidació dels quals varia depenent del tipus de substituent del nitrogen indòlic. A partir d'un substrat convenientment substituït s'ha assolit la síntesi de l'alcaloide calotrixina B. - El desenvolupament d'un protocol "metal free" per a la ciclació de radicals 3-(3-quinolil)metil-2-indolilacil, en el qual es fa evident la importància del paper de l'AIBN en les reaccions de substitució homolítica aromàtica.[eng] This thesis work is placed in the context of intramolecular reactions of 2- indolylacyl radicals. According with the initial objectives it's structured in two parts. The first part focus attention to the cyclisation of 2-indolylacyl radicals under reductive conditions, using alkenes as radical acceptors to obtain structures related with natural products and medicinal compounds. In this first part: - A new annulation procedure based on intramolecular reactions of 2- indolylacyl radicals have been developed. This procedure provides straightforward access to cyclic ketones fused to 1,2-position of the indole nucleus. - A total synthesis of the (±)-guatambuine and a formal synthesis of Olivacine alkaloid have been achieved. The second part of the work is placed in the context of intramolecuar reactions of 2-indolylacyl radicals with aromatic systems. In this second part: - The cyclization of 2-indolylacyl radicals under non reductive conditions (n-Bu6Sn2-h"v"to give efficiently tetracyclic phenyl indolyl ketones have been studied. - Regioselective cyclization of 2-indolylacyl radicals upon pyridines under non reductive conditions (n-Bu6Sn2-h"v" to give tetracyclic indolyl 4-pyridyl ketones have been studied. The effectiveness of this radical protocol is illustrated by a fast synthetic entry to ellipticine quinones. - The cyclisation of 3-(3-quinolyl)methyl-2-indolylacyl radicals under TTMSS-AIBN conditions have been studied. This cyclisation provides an efficient synthetic entry to calothrixin-related pentacycles, which are obtained in a different oxidation state depending on the substitution at the indole nitrogen. The synthesis of calothrixin B has been achieved from a radical precursor suitably protected at the indole nitrogen. - A new metal-free protocol for the cyclisation of 3-(3-quinolyl)methyl-2- indolylacyl radicals that illustrates the determinant role of AIBN in homolytic aromatic substitutions have been developed
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Reaccions intramolecualrs de radicals 2-indolilacil: aplicació a la síntesi de compostos indòlics
'Edicions de la Universitat de Barcelona', 2006Co-Authors: Ferrando Ruana FrancescAbstract:La present Tesi Doctoral es situa en el context de les reaccions intramoleculars de radicals 2-indolilacil i està constituïda, d'acord amb els objectius inicials, per dues parts.La primera part centra l'atenció en les ciclacions de radicals 2-indolilacil en condicions reductores, emprant alquens com a acceptors radicalaris per a l'obtenció d'estructures que formen part de productes naturals i d'altres compostos bioactius.En aquest context s'ha aconseguit: - El desenvolupament d'un nou procediment d'anulació indòlica que permet accedir a cetones cícliques 1,2-fusionades amb l'indole.- La síntesi total de l'alcaloide (±)-guatambuïna i la síntesi formal de l'alcaloide olivacina.La segona part es situa en el context de les reaccions intramoleculars de radicals 2-indolilacil amb sistemes aromàtics.Els principals aconseguiments en aquesta part són:- La ciclació de radicals 2-indolilacil sobre anells de benzè en condicions no reductores (n-Bu6Sn2-hvper donar de manera eficient indolil fenil cetones tetracícliques.- La ciclació regioselectiva de radicals 2-indolilacil sobre piridines en condicions no reductores (n-Bu6Sn2-hv per donar indolil 4-piridil cetones tetracícliques. L'efectivitat d'aquest protocol radicalari permet el fàcil accés a elipticina quinones.- La ciclació de radicals 3-(3-quinolil)metil-2-indolilacil en condicions reductores (TTMSS-AIBN) per donar pentacicles relacionats amb la calotrixina, l'estat d'oxidació dels quals varia depenent del tipus de substituent del nitrogen indòlic. A partir d'un substrat convenientment substituït s'ha assolit la síntesi de l'alcaloide calotrixina B.- El desenvolupament d'un protocol "metal free" per a la ciclació de radicals 3-(3-quinolil)metil-2-indolilacil, en el qual es fa evident la importància del paper de l'AIBN en les reaccions de substitució homolítica aromàtica.This thesis work is placed in the context of intramolecular reactions of 2- indolylacyl radicals. According with the initial objectives it's structured in two parts.The first part focus attention to the cyclisation of 2-indolylacyl radicals under reductive conditions, using alkenes as radical acceptors to obtain structures related with natural products and medicinal compounds.In this first part:- A new annulation procedure based on intramolecular reactions of 2- indolylacyl radicals have been developed. This procedure provides straightforward access to cyclic ketones fused to 1,2-position of the indole nucleus.- A total synthesis of the (±)-guatambuine and a formal synthesis of Olivacine alkaloid have been achieved.The second part of the work is placed in the context of intramolecuar reactions of 2-indolylacyl radicals with aromatic systems.In this second part:- The cyclization of 2-indolylacyl radicals under non reductive conditions (n-Bu6Sn2-h"v"to give efficiently tetracyclic phenyl indolyl ketones have been studied.- Regioselective cyclization of 2-indolylacyl radicals upon pyridines under non reductive conditions (n-Bu6Sn2-h"v" to give tetracyclic indolyl 4-pyridyl ketones have been studied. The effectiveness of this radical protocol is illustrated by a fast synthetic entry to ellipticine quinones.- The cyclisation of 3-(3-quinolyl)methyl-2-indolylacyl radicals under TTMSS-AIBN conditions have been studied. This cyclisation provides an efficient synthetic entry to calothrixin-related pentacycles, which are obtained in a different oxidation state depending on the substitution at the indole nitrogen. The synthesis of calothrixin B has been achieved from a radical precursor suitably protected at the indole nitrogen.- A new metal-free protocol for the cyclisation of 3-(3-quinolyl)methyl-2- indolylacyl radicals that illustrates the determinant role of AIBN in homolytic aromatic substitutions have been developed.
Ivo Jose Curcino Vieira - One of the best experts on this subject based on the ideXlab platform.
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two new indole alkaloids from tabernaemontana hystrixsteud apocynaceae
Helvetica Chimica Acta, 2010Co-Authors: Jucimar Jorgeane De Souza, Leda Mathias, Raimundo Brazfilho, Ivo Jose Curcino VieiraAbstract:Two new monoterpene indole alkaloids named ibogamine-7,8-dione (1) and 12-methoxyvoachalotine (2), and eight known ones, coronaridine (3), coronaridine hydroxyindolenine (4), 5-oxocoronaridine (5), 3-oxocoronaridine hydroxyindolenine (6), 3-oxocoronaridine (7), vobasine (8), ibogamine (9), and Olivacine (10), were isolated from a CH2Cl2 extract of the root bark from Tabernaemontana hystrix. The structures of the compounds were elucidated on the basis of spectroscopic data analyses, mainly 1H- and 13C-NMR, including 2D experiments (1H,1H-COSY, HMBC, and HMQC).
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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 Jose Curcino Vieira, Walter L.b. Medeiros, Raimundo Braz-filho, Angelo C. Pinto, Priscila Mesquita De Sousa, Claudia M. Rezende, Jucimar Jorgeane De Souza, Cecilia Silva Monnerat, Leda Mathias, 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 Jose Curcino Vieira, Walter L.b. Medeiros, Raimundo Braz-filho, Angelo C. Pinto, Priscila Mesquita De Sousa, Claudia M. Rezende, Jucimar Jorgeane De Souza, Cecilia Silva Monnerat, Leda Mathias, 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
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a new indole alkaloid isolated from tabernaemontana hystrix steud apocynaceae
Journal of the Brazilian Chemical Society, 2005Co-Authors: Cecilia Silva Monnerat, Jucimar Jorgeane De Souza, Leda Mathias, Raimundo Brazfilho, Ivo Jose Curcino VieiraAbstract:Um novo alcaloide, denominado histrixnina (1), e cinco alcaloides indolicos conhecidos, ibogamina (2), olivacina (3) e affinina (4), affinisina (5) e Nb-metilaffinisina (6), foram isolados do extrato metanolico das cascas das raizes de Tabernaemontana hystrix. Os triterpenos conhecidos 3-O-acetil-a-amirina, 3-O-acetil-b-amirina, 3-O-acetil-lupeol foram tambem identificados. As estruturas dos compostos foram elucidadas com base na analise de dados espectroscopicos.
Jucimar Jorgeane De Souza - One of the best experts on this subject based on the ideXlab platform.
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two new indole alkaloids from tabernaemontana hystrixsteud apocynaceae
Helvetica Chimica Acta, 2010Co-Authors: Jucimar Jorgeane De Souza, Leda Mathias, Raimundo Brazfilho, Ivo Jose Curcino VieiraAbstract:Two new monoterpene indole alkaloids named ibogamine-7,8-dione (1) and 12-methoxyvoachalotine (2), and eight known ones, coronaridine (3), coronaridine hydroxyindolenine (4), 5-oxocoronaridine (5), 3-oxocoronaridine hydroxyindolenine (6), 3-oxocoronaridine (7), vobasine (8), ibogamine (9), and Olivacine (10), were isolated from a CH2Cl2 extract of the root bark from Tabernaemontana hystrix. The structures of the compounds were elucidated on the basis of spectroscopic data analyses, mainly 1H- and 13C-NMR, including 2D experiments (1H,1H-COSY, HMBC, and HMQC).
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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 Jose Curcino Vieira, Walter L.b. Medeiros, Raimundo Braz-filho, Angelo C. Pinto, Priscila Mesquita De Sousa, Claudia M. Rezende, Jucimar Jorgeane De Souza, Cecilia Silva Monnerat, Leda Mathias, 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 Jose Curcino Vieira, Walter L.b. Medeiros, Raimundo Braz-filho, Angelo C. Pinto, Priscila Mesquita De Sousa, Claudia M. Rezende, Jucimar Jorgeane De Souza, Cecilia Silva Monnerat, Leda Mathias, 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
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a new indole alkaloid isolated from tabernaemontana hystrix steud apocynaceae
Journal of the Brazilian Chemical Society, 2005Co-Authors: Cecilia Silva Monnerat, Jucimar Jorgeane De Souza, Leda Mathias, Raimundo Brazfilho, Ivo Jose Curcino VieiraAbstract:Um novo alcaloide, denominado histrixnina (1), e cinco alcaloides indolicos conhecidos, ibogamina (2), olivacina (3) e affinina (4), affinisina (5) e Nb-metilaffinisina (6), foram isolados do extrato metanolico das cascas das raizes de Tabernaemontana hystrix. Os triterpenos conhecidos 3-O-acetil-a-amirina, 3-O-acetil-b-amirina, 3-O-acetil-lupeol foram tambem identificados. As estruturas dos compostos foram elucidadas com base na analise de dados espectroscopicos.
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A new indole alkaloid isolated from Tabernaemontana hystrix steud (Apocynaceae)
Sociedade Brasileira de Química, 2005Co-Authors: Monnerat, Cecilia Silva, Mathias Leda, Braz-filho Raimundo, Jucimar Jorgeane De Souza, Vieira, Ivo José C.Abstract:A new alkaloid, named hystrixnine (1), and five known indole alkaloids, ibogamine (2), Olivacine (3), affinine (4), affinisine (5) and Nb-methylaffinisine (6), were isolated from the root bark of Tabernaemontana hystrix. The known triterpenes alpha-amyrin acetate, beta-amyrin acetate and lupeol acetate were also identified. The structures of the compounds were elucidated based on spectroscopic studies.Um novo alcalóide, denominado histrixnina (1), e cinco alcalóides indólicos conhecidos, ibogamina (2), olivacina (3) e affinina (4), affinisina (5) e Nb-metilaffinisina (6), foram isolados do extrato metanólico das cascas das raízes de Tabernaemontana hystrix. Os triterpenos conhecidos 3-O-acetil-alfa-amirina, 3-O-acetil-beta-amirina, 3-O-acetil-lupeol foram também identificados. As estruturas dos compostos foram elucidadas com base na análise de dados espectroscópicos
Francesc Ferrando - One of the best experts on this subject based on the ideXlab platform.
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regioselective 6 endo cyclizations of 2 indolylacyl radicals total synthesis of the pyrido 4 3 b carbazole alkaloid guatambuine
Journal of Organic Chemistry, 2006Co-Authors: Lluisa M Bennasar, Tomas Roca, Francesc FerrandoAbstract:A regioselective 6-endo reductive cyclization of 2-indolylacyl radicals constitutes the key step of a straightforward synthetic entry to the Olivacine skeleton, illustrated by a total synthesis of the tetrahydropyridine alkaloid guatambuine.
Gracielle Rodrigues Dantas - One of the best experts on this subject based on the ideXlab platform.
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comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine Olivacine cryptolepine and a synthetic cryptolepine analog
Phytomedicine, 2012Co-Authors: L Rocha F E Silva, A Montoia, Rodrigo C N Amorim, Marcia R S Melo, Marycleuma Campos Henrique, Sergio Massayoshi Nunomura, Monica R F Costa, V Andrade F Neto, Debhora Geny De Sousa Costa, Gracielle Rodrigues DantasAbstract:Indole alkaloids ellipticine (1), cryptolepine triflate (2a), rationally designed 11-(4-piperidinamino)cryptolepine hydrogen dichloride (2b) and Olivacine (3) (an isomer of 1) were evaluated in vitro against Plasmodium falciparum and in vivo in Plasmodium berghei-infected mice. 1-3 inhibited P. falciparum (IC₅₀≤1.4 μM, order of activity: 2b>1>2a>3). In vitro toxicity to murine macrophages was evaluated and revealed selectivity indices (SI) of 10-12 for 2a and SI>2.8×10² for 1, 2b and 3. 1 administered orally at 50mg/kg/day was highly active against P. berghei (in vivo inhibition compared to untreated control (IVI)=100%, mean survival time (MST)>40 days, comparable activity to chloroquine control). 1 administered orally and subcutaneously was active at 10 mg/kg/day (IVI=70-77%; MST=27-29 days). 3 exhibited high oral activity at ≥50 mg/kg/day (IVI=90-97%, MST=23-27 days). Cryptolepine (2a) administered orally and subcutaneously exhibited moderate activity at 50mg/kg/day (IVI=43-63%, MST=24-25 days). At 50 mg/kg/day, 2b administered subcutaneously was lethal to infected mice (MST=3 days) and moderately active when administered orally (IVI=45-55%, MST=25 days). 1 and 3 are promising compounds for development of antimalarials.
