title: Studies on chemical structure modification and biology of a natural product, gambogic acid (I): Synthesis and biological evaluation of oxidized analogues of gambogic acid.
abstract: Gambogic acid (GA), a natural product, exhibits high potency in inhibiting cancer cell growth through the effective induction of apoptosis. In order to investigate the structure-activity relationships of GA derivatives, 11 oxidized derivatives of GA were synthesized. Some of them showed strong inhibitory effects on HT-29, Bel-7402, BGC-823, A549, and SKOV 3 cell lines. Moreover, in this paper the cellular growth inhibitor 39-hydroxy-6-methoxy-gambogic acid methyl ester (10) was identified as a HepG2 cell apoptosis inhibitor through Annexin-V/PI double staining assay and the expression of the related apoptotic proteins (Bax and Bcl-2). Compound 10 may serve as a potential lead compound for the development of new anticancer drugs. Further SAR studies of GA derivatives indicated that modification of carbon-carbon double bond at C-32/33 or C-37/38 and of the methyl groups at C-39/C-35 can improve antitumor activity.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jinxin
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.forename: Nianguang
authors.initials: N
authors.lastname: Li
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001685:Biological Factors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D044004:Xanthones; C052659:gambogic acid