Synthesis and evaluation of in vitro antimycobacterial activity of novel 1H-benzo[d]imidazole derivatives and analogues

•We synthesized a new series of benzimidazoles.•Compounds were tested against M. tuberculosis and M. bovis in vitro.•Some compounds exhibited excellent tuberculostatic activity.•Cytotoxic activity towards eukaryotic cells was determined.•Two derivatives were characterized by high therapeutic index in vitro.

A series of novel 1H-benzo[d]imidazole derivatives and analogues (1–25) have been synthesized and evaluated for tuberculostatic activity. Benzimidazoles substituted at the C-2 position with cyclohexylethyl, cyclohexylpropyl and phenylpropyl moiety or 4-phenylpyridine system were obtained. Compounds 3, 4, 6 and 7 bearing halogen atoms or methyl groups at the benzimidazole system and cyclohexylethyl substituent at the C-2 position showed an excellent tuberculostatic activity against Mycobacterium tuberculosis and Mycobacterium bovis strains with MIC values ranging from 0.75 to 1.5 μg/mL. More importantly, derivatives 4 (5-Bromo-2-(2-cyclohexylethyl)-1H-benzo[d]imidazole) and 6 (2-(2-cyclohexylethyl)-5,6-dimethyl-1H-benzo[d]imidazole) appeared selective for M. tuberculosis and M. bovis as compared with non-malignant eukaryotic cells (LLC-PK1 pig kidney epithelial cell line). These compounds may thus represent a novel, selective class of anti-tubercular agents.

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