title: Synthesis of novel 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds and their evaluation for tuberculostatic activity.
abstract: A series of novel 3-cyclohexylpropanoic acid derivatives and 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds (1-8) have been synthesized and evaluated for tuberculostatic activity. Compounds 1a, 1c, 1e and 1f bearing benzimidazole or benzimidazole-like systems showed the most potent tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 1.5 to 12.5μg/mL. More importantly 1a (6-chloro-2-(2-cyclohexylethyl)-4-nitro-1H-benzo[d]imidazole) and 1f (2-(2-cyclohexylethyl)-1H-imidazo[4,5-b]phenazine) appeared selective for M. tuberculosis as compared with eukaryotic cells (human fibroblasts), and other antimicrobial strains. These compounds may thus represent a novel, selective class of antitubercular agents. Additionally compound 1a stimulated type I collagen output by fibroblasts, in vitro.
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland. kgobis@gumed.edu.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gobis
authors.forename: Henryk
authors.initials: H
authors.lastname: Foks
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bojanowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Napiórkowska
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry; D002460:Cell Line; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011422:Propionates / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D001562:Benzimidazoles; D006571:Heterocyclic Compounds; D011422:Propionates; C031000:benzimidazole