The structures of benzimidazole derivatives and their potential as tuberculostatics

Abstract

Tuberculosis still remains a very important problem, especially its multidrug resistant varieties (MDR-TB). Among the potential tuberculostatics, there are two benzimidazole derivatives, namely 5,6-dimethyl-2-phenylethylbenzo[d]imidazole (1) and (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazole (2) which showed significant tuberculostatic activities, better than those of Pyrazinamide and Isoniazyd. Also, the cytotoxicity of 1 appeared promising. The compounds were studied (with the use of X-ray diffraction) in the form of the hemihydrate of 1, C17H18N2·0.5H2O (1a), the methanol hemisolvate of 2, C17H16N2·0.5CH3OH (2a), and the acid oxalate salt of 2, namely (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazolium hydrogen oxalate, C17H17N2 +·C2HO4 − (2b). All three structures reveal a similar extended conformation, despite the flexible linker between the two aromatic systems and the different types of strong intermolecular hydrogen bonds. The molecules of 2a are practically planar due to the double bond in the linker, which enables conjugation along the whole molecule, while the molecules of 1a exhibit the possibility of parallel orientations of their aromatic systems, despite the aliphatic (ethyl) linker.

Structure and Microbiological Activity of 1H-benzo[d]imidazole Derivatives

“…In the CSD (Cambridge Structural Database) [ 20 ], there is only one analogous structure, with code HIQXIR [ 21 ]. It has a phenyl end group and an ethyl linker (CH 2 -CH 2 ).…”

Novos medicamentos para o tratamento da tuberculose pulmonar

“…Segundo a Organização Mundial de Saúde (OMS), esta doença supera o número de casos de infecção e óbito pelo vírus da imunodeficiência humana (HIV). Além disso, apresentouse como a segunda doença que mais mata a nível global, causada por um único agente infeccioso, após a COVID-19 ( Devido a quantidade de novos casos notificados e subnotificados, a busca por novos tuberculostáticos ainda é um assunto importante (GŁÓWKA M, et al, 2018). O processo de quimioterapia da TB, iniciado na década de 40, sofreu alterações e combinações ao longo dos anos, devido a constatação de resistência das cepas aos medicamentos (DA SILVA Jr, 2020).…”