title: Synthesis and biological evaluation of novel derivatives of gambogic acid as anti-hepatocellular carcinoma agents.
abstract: A series of novel derivatives of gambogic acid (GA) were synthesized and evaluated for their in vitro cytotoxicity against human hepatocellular carcinoma (HCC) cells. All derivatives showed better aqueous solubility than GA, and compounds 3a, 3e, and 3f displayed potent inhibition of HCC cell proliferation (IC(50): 0.045-0.59 μM on Bel-7402 cells and 0.067-0.94 μM on HepG2 cells) superior to GA and taxol. Additionally, the most potent compound 3e did not affect significantly the proliferation of non-tumor liver cells, suggesting that it might selectively inhibit HCC proliferation. Furthermore, 3e induced high frequency of Bel-7402 cell apoptosis. Our findings suggest that these novel GA derivatives may hold a great promise as therapeutic agents for the intervention of human HCC.
authors.affiliation: Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Liqin
authors.initials: L
authors.lastname: He
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Dengke
authors.initials: D
authors.lastname: Yin
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Wang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy*; D008956:Models, Chemical; D012995:Solubility; D044004:Xanthones / Q000737:chemistry*
chemical_list: D044004:Xanthones; C052659:gambogic acid