Article
Anti-Tuberculosis Evaluation and Conformational Study of N-Acylhydrazones Containing the Thiophene Nucleus
Registro en:
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.
0365-6233
10.1002/ardp.201300417
Autor
Cardoso, Laura Nogueira de Faria
Bispo, Marcelle de Lima Ferreira
Kaiser, Carlos Roland
Wardell, James L.
Wardell, Solange M. S. V.
Lourenço, Maria Cristina da Silva
Bezerra, Flávio A. F. M.
Soares, Rodrigo Pedro Pinto
Rocha, Marcele Neves
Souza, Marcus Vinícius Nora de
Resumen
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.