title: Synthesis and evaluation of in vitro antimycobacterial activity of novel 1H-benzo[d]imidazole derivatives and analogues.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland. Electronic address: kgobis@gumed.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gobis
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Foks
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, 11/12 G. Narutowicza Str., 80-233 Gdańsk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Serocki
authors.affiliation: Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka Str., 01-138 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
authors.affiliation: Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka Str., 01-138 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Napiórkowska
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009163:Mycobacterium bovis / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000995:Antitubercular Agents; D001562:Benzimidazoles
keywords: Benzimidazole; Cytotoxicity; SAR-study; Synthesis; Tuberculostatic activity