title: Design and synthesis of novel benzimidazole derivatives as anti-tuberculosis agents.
abstract: In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Zhang
authors.forename: Zi-Yun
authors.initials: ZY
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Huang
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001562:Benzimidazoles; C031000:benzimidazole; C027391:2-aminobenzimidazole