Search
Close this search box.

Anti-Tuberculosis Evaluation and Conformational Study of N -Acylhydrazones Containing the Thiophene Nucleus.

Authors: Cardoso, L.N.F.; Bispo, M.L.F.; Kaiser, C.R.; Wardell, J.L.; Wardell, S.M.S.V.; Lourenço, M.C.S.; Bezerra, F.A.F.M.; Soares, R.P.P. Rocha, M.N.; De Souza, M.V.N.


Abstract

A series of N-acylhydrazonyl-thienyl derivatives (compounds 2 and 3), mainly of the type 2-(aryl-CH[DOUBLE BOND]N[BOND]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[DOUBLE BOND]N and ZC(O)N/EC[DOUBLE BOND]N conformers.
Keywords: Antimycobacterial activity; Conformational study; N-Acylhydrazones; Thiophene; Tuberculosis Document Type: Research Article DOI: http://dx.doi.org/10.1002/ardp.201300417 Publication date: 10 de Março de 2014

Compartilhar publicação

Facebook
Twitter
Email
LinkedIn
WhatsApp

Deixe seu comentário

Compartilhar

Sobre a SSCDT

Nosso grupo de pesquisa está situado em Farmanguinhos e atualmente é o maior laboratório farmacêutico oficial vinculado ao Ministério da Saúde. Farmanguinhos produz mais de um bilhão de medicamentos por ano para os programas estratégicos do Governo Federal, além de atender demandas emergenciais no Brasil e no exterior.

posts Recentes