Novel 2-(2-phenalkyl)-1H-benzo[d]imidazoles as antitubercular agents. Synthesis, biological evaluation and structure-activity relationship

Bioorganic & Medicinal Chemistry
Katarzyna GobisKrzysztof Bojanowski

Abstract

A series of novel 2-(2-phenalkyl)-1H-benzo[d]imidazole derivatives and analogues (2a-3l) have been synthesized and evaluated for tuberculostatic activity. Benzimidazoles substituted at the C-2 position with phenethyl, styryl and 3,5-dichlorophenethyl moiety were obtained. Compounds 2g, 2h and 2i bearing methyl groups at the benzimidazole system and phenalkyl substituent at the C-2 position showed high tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 0.8 to 6.2 μg/mL (2.5-25 μM). More importantly, derivatives 2g (5,6-dimethyl-2-phenethyl-1H-benzo[d]imidazole) and 2i (2-(3,5-dichlorophenethyl)-5,6-dimethyl-1H-benzo[d]imidazole) appeared selective for M. tuberculosis as compared with eukaryotic cells: non-malignant (neonatal human dermal fibroblasts) and malignant (mouse melanoma B16-F10 cell line). These compounds may thus represent a novel, selective class of anti-tubercular agents. SAR studies resulted in interesting conclusions on structural factors affecting tuberculostatic activity.

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Citations

Jun 10, 2017·Medicinal Research Reviews·Vajinder KumarRahul Jain
Dec 6, 2018·Acta Crystallographica. Section C, Structural Chemistry·Marek L GłówkaAndrzej Olczak
Jul 25, 2019·Antimicrobial Agents and Chemotherapy·Małgorzata Korycka-MachałaJarosław Dziadek
Jul 7, 2020·Acta Crystallographica. Section C, Structural Chemistry·Małgorzata SzczesioAndrzej Olczak
Apr 25, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Malwina KrauseKatarzyna Gobis
Jun 8, 2017·Pharmaceuticals·Guilherme Felipe Dos Santos FernandesJean Leandro Dos Santos
Dec 23, 2020·Bioorganic Chemistry·Tejas M DhameliyaAsit K Chakraborti
Dec 21, 2019·ACS Infectious Diseases·Clément RaynaudLaurent Kremer

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