A duplicated nitrotienyl derivative with antimycobacterial activity: synthesis, X-ray crystallography, biological and mutagenic activity tests

D G Rando; A C Doriguetto; C H Tomich de Paula da Silva; J Ellena; D N Sato; C Q F Leite; E A Varanda; E I Ferreira

doi:10.1016/j.ejmech.2006.04.009

A duplicated nitrotienyl derivative with antimycobacterial activity: synthesis, X-ray crystallography, biological and mutagenic activity tests

Eur J Med Chem. 2006 Oct;41(10):1196-200. doi: 10.1016/j.ejmech.2006.04.009. Epub 2006 Jul 7.

Authors

D G Rando¹, A C Doriguetto, C H Tomich de Paula da Silva, J Ellena, D N Sato, C Q F Leite, E A Varanda, E I Ferreira

Affiliation

¹ Faculdade de Ciências Farmacêuticas, Universidade de São Paulo - Av. Prof. Lineu Prestes, 580, CEP 05508-900, São Paulo, SP, Brazil.

PMID: 16828526
DOI: 10.1016/j.ejmech.2006.04.009

Abstract

A duplicated nitrotienyl derivative was obtained as a by-product from the synthesis of a proposed molecular hybrid of a nitrotienyl derivative and isoniazid with an expected dual antimycobacteria mechanism. The structure was shown to be the 5,5'-dinitro-2-(2,3-diaza-4-(2'-tienyl)buta-1,3-dienyl)tiophene by X-ray crystallography. The minimal inhibitory concentration (MIC) determination of this compound proved to be promising against Mycobacterium pathogenic strains such as M. avium and M. kansasii, although it had a high level of mutagenicity, as observed in mutagenic activity tests.

MeSH terms

Antitubercular Agents / chemical synthesis*
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology*
Crystallography, X-Ray
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Mycobacterium avium / drug effects*
Mycobacterium kansasii / drug effects*
Nitro Compounds / chemical synthesis*
Nitro Compounds / chemistry
Nitro Compounds / pharmacology*
Structure-Activity Relationship
Thiophenes / chemical synthesis*
Thiophenes / chemistry
Thiophenes / pharmacology*

Substances

5,5'-dinitro-2-(2,3-diaza-4-(2'-tienyl)buta-1,3-dienyl)tiophene
Antitubercular Agents
Nitro Compounds
Thiophenes