title: Novel 2-(2-phenalkyl)-1H-benzo[d]imidazoles as antitubercular agents. Synthesis, biological evaluation and structure-activity relationship.
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.
authors: Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland. Electronic address: kgobis@gumed.edu.pl.
authors: Katarzyna
authors: K
authors: Gobis
authors: Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland.
authors: Henryk
authors: H
authors: Foks
authors: Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland.
authors: Karolina
authors: K
authors: Suchan
authors: Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka Str., 01-138 Warsaw, Poland.
authors: Ewa
authors: E
authors: Augustynowicz-Kopeć
authors: Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka Str., 01-138 Warsaw, Poland.
authors: Agnieszka
authors: A
authors: Napiórkowska
authors: Sunny BioDiscovery Inc., 722 East Main Str., Santa Paula, CA 93060, USA.
authors: Krzysztof
authors: K
authors: Bojanowski
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; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001562:Benzimidazoles
keywords: Anti-proliferative activity; Benzimidazole; SAR-study; Synthesis; Tuberculostatic activity