Design and synthesis of novel benzimidazole derivatives as anti-tuberculosis agents.
- Author:
Hui-Ying ZHANG
;
Bin WANG
;
Li SHENG
;
Dan LI
;
Dong-Feng ZHANG
;
Zi-Yun LIN
;
Yu LU
;
Yan LI
;
Hai-Hong HUANG
- Publication Type:Journal Article
- MeSH:
Antitubercular Agents;
pharmacology;
Benzimidazoles;
chemistry;
pharmacology;
Drug Design;
Humans;
Structure-Activity Relationship;
Tuberculosis;
drug therapy
- From:
Acta Pharmaceutica Sinica
2014;49(5):644-651
- CountryChina
- Language:English
-
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.
