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Synthesis and Anti‐tumor Evaluation of Novel C‐37 Modified Derivatives of Gambogic Acid
Author(s) -
Li Xiang,
Zhang Xiaojin,
Sun Haopeng,
Zhang Lei,
Gao Yuan,
Wang Jinxin,
Guo Qinglong,
You Qidong
Publication year - 2012
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201100693
Subject(s) - gambogic acid , chemistry , lead compound , tumor cells , in vitro , a549 cell , cell culture , stereochemistry , structure–activity relationship , combinatorial chemistry , biochemistry , cancer research , genetics , biology
Abstract 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, compound 8 was almost 5–10 folds more active than GA against A549 and BGC‐823 cell lines with the IC 50 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.