Author | Cardoso, Laura Nogueira de Faria | |
Author | Bispo, Marcelle de Lima Ferreira | |
Author | Kaiser, Carlos Roland | |
Author | Wardell, James L. | |
Author | Wardell, Solange M. S. V. | |
Author | Lourenço, Maria Cristina da Silva | |
Author | Bezerra, Flávio A. F. M. | |
Author | Soares, Rodrigo Pedro Pinto | |
Author | Rocha, Marcele Neves | |
Author | Souza, Marcus Vinícius Nora de | |
Access date | 2015-07-13T14:06:48Z | |
Available date | 2015-07-13T14:06:48Z | |
Document date | 2014 | |
Citation | CARDOSO, Laura Nogueira de Faria et al. Anti-Tuberculosis Evaluation and Conformational Study of N-Acylhydrazones Containing the Thiophene Nucleus. Archiv der Pharmazie / Chemistry in Life Sciences, v. 347, n. 6, p. 432-448, 2014. | pt_BR |
ISSN | 0365-6233 | |
URI | https://www.arca.fiocruz.br/handle/icict/11231 | |
Language | eng | pt_BR |
Publisher | Verlag Chemie GmbH | pt_BR |
Rights | restricted access | pt_BR |
Title | Anti-Tuberculosis Evaluation and Conformational Study of N-Acylhydrazones Containing the Thiophene Nucleus | pt_BR |
Type | Article | pt_BR |
DOI | 10.1002/ardp.201300417 | |
Abstract | A series of N-acylhydrazonyl-thienyl derivatives (compounds 2 and 3), mainly of the type 2-(aryl-CH=N-NHCOCH2 )-thiene (2: aryl = substituted-phenyl; 3: aryl = heteroaryl) were evaluated against Mycobacterium tuberculosis. Particularly active compound was 3 (heteroaryl = 5-nitrothien-2-yl or 5-nitrofuran-2-yl) with MIC values of 8.5 and 9.0 μM, respectively. Moderately active compounds were compound 3 (heteroaryl = pyridin-2-yl) and compound 2 containing aryl = 2- or 4-hydroxyphenyl groups, with MIC values between 170 and 408 μM. Compound 2 containing OMe, H, F, Cl, Br, CN, and NO2 substituents and compound 3 (heteroaryl = furan-2-yl, thien-2-yl, pyrrol-2-yl, imidazol-2-yl, pyridin-3-yl, and pyridin-4-yl) were all inactive. Clearly, there is no correlation of activity with the electronic effects of the substituents. The activities suggest different modes of biological action of the compounds having nitro-heteroaryl groups, on the one hand, and the 2-hydroxyphenyl or pyridin-2-yl substituents, on the other hand. Compounds having 2- or 4-hydroxyphenyl, 2-hydroxy-5-nitrophenyl, or 4-hydroxy-3-chlorophenyl were less cytotoxic than ethambutol. It is important to notice that compound 3 (aryl = 5-NO2 -furan-2-yl) exhibited a promising therapeutic index (TI = 1093.90), with a value 4.4 less than that of ethambutol. Compounds 2 and 3 exist in DMSO or MeOD solutions as mixtures of EC(O)N /EC=N and ZC(O)N /EC=N conformers. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Department of Chemistry, University of Aberdeen, Old Aberdeen, Scotland. | pt_BR |
Affilliation | Department of Chemistry, University of Aberdeen, Old Aberdeen, Scotland. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Pesquisas Clínicas Evandro Chagas. Departamento de Bacteriologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Pesquisas Clínicas Evandro Chagas. Departamento de Bacteriologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Antimycobacterial activity | pt_BR |
Subject | Conformational study | pt_BR |
Subject | N-Acylhydrazones | pt_BR |
Subject | Thiophene | pt_BR |
Subject | Tuberculosis | pt_BR |