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.