title: Synthesis, structure-activity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives.
abstract: Twenty-eight new 13-n-octylberberine derivatives were synthesized and evaluated for their activities against drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) strain H(37)Rv. Among these compounds, compound 16e was the most effective anti-tubercular agent with a MIC value of 0.125 μg/mL. Importantly, compound 16e exhibited more potent effect against rifampicin (RIF)- and isoniazid (INH)-resistant M. tuberculosis strains than both RIF and INH, suggesting a new mechanism of action. Therefore, it has been selected as a drug candidate for further investigation, or as a chemical probe for identifying protein target and studying tuberculosis biology. We consider 13-n-octylberberine analogs to be a promising novel class of antituberculars against multi-drug-resistant (MDR) strains of M. tuberculosis.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Liu
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Xiao
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Yang
authors.forename: Yang-Biao
authors.initials: YB
authors.lastname: Li
authors.forename: Chong-Wen
authors.initials: CW
authors.lastname: Bi
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Gao
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C574517:13-n-octylberberine; D000900:Anti-Bacterial Agents; D001599:Berberine