Synthesis and Anti-tumor Evaluation of Novel C-37 Modified Derivatives of Gambogic Acid  

作　　者：李想 张晓进 孙昊鹏 张磊 高原 王进欣 郭青龙 尤启冬 

机构地区：[1]State Key Laboratory of Natural Medicines(China Pharmaceutical University),Nanjing,Jiangsu 210009,China [2]Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing,Jiangsu 21009,China [3]Jiangsu Key Laboratory of Carcinogenesis and lntervention,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Chinese Journal of Chemistry》2012年第5期1083-1091,共9页中国化学（英文版）

基　　金：Acknowledgement This work was supported by the National Natural Science Foundation of China （Nos. 90713038, 21072231, 30873157） and National Major Science and Technology Project of China （Innovation and Development of New Drugs. Nos. 2008ZX09401-001, 2009ZX09501-003）.

摘　　要：Gambogic acid （GA, 1）, the most prominent representative of Garcinia natural products, has been reported to be a promising anti-tumor agent. In order to further explore the structure-activity relationship of GA and discover novel GA derivatives as anti-tumor agents, 17 novel C-37 modified derivatives of GA were synthesized and evaluated for their in vitro anti-tumor activities against A549, HCT-116, BGC-823, HepG2 and MCF-7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, com- pound 8 was almost 5--10 folds more active than GA against A549 and BGC-823 cell lines with the IC50 values of 0.12 μmol·L^-1 and 0.57 μmol·L^-1, respectively. Chemical modification at C-37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug-like properties. These findings will enhance our understanding of the structure-activity relationship （SAR） of GA and lead to the discovery of novel GA derivatives as potential anti-tumor agents.Gambogic acid （GA, 1）, the most prominent representative of Garcinia natural products, has been reported to be a promising anti-tumor agent. In order to further explore the structure-activity relationship of GA and discover novel GA derivatives as anti-tumor agents, 17 novel C-37 modified derivatives of GA were synthesized and evaluated for their in vitro anti-tumor activities against A549, HCT-116, BGC-823, HepG2 and MCF-7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, com- pound 8 was almost 5--10 folds more active than GA against A549 and BGC-823 cell lines with the IC50 values of 0.12 μmol·L^-1 and 0.57 μmol·L^-1, respectively. Chemical modification at C-37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug-like properties. These findings will enhance our understanding of the structure-activity relationship （SAR） of GA and lead to the discovery of novel GA derivatives as potential anti-tumor agents.

关 键 词：gambogic acid C-37 modified derivatives anti-tumor activity structure-activity relationship （SAR） 

分 类 号：TQ252.3[化学工程—有机化工] O636.1[理学—高分子化学]