Synthesis, structure-activity relationship and in?vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives

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• 作者：Yan-Xin Liu¹ ; Chun-Ling Xiao¹ ; Yan-Xiang Wang ; Ying-Hong Li ; Yan-Hui Yang ; Yang-Biao Li ; Chong-Wen Bi ; Li-Mei Gao ; Jian-Dong Jiang ; ^{jiang.jdong@163.com} ; Dan-Qing Song ; ^{songdanqingsdq@hotmail.com}
• 关键词：13-n-Octylberberine ; Antitubercular ; Structure&ndash ; activity relationship ; MIC ; Drug-resistance
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：52
• 期：Complete
• 页码：151-158
• 全文大小：281 K

文摘

Twenty-eight new 13-n-octylberberine derivatives were synthesized and evaluated for their activities against drug-susceptible Mycobacterium tuberculosis (M.?tuberculosis) strain H₃₇Rv. Among these compounds, compound 16e was the most effective anti-tubercular agent with a MIC value of 0.125?¦Ìg/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.