Stability and cytotoxicity of gambogic acid and its derivative, gambogoic acid.
In this study, the stability of gambogic acid (GA), a polyprenylated xanthone with potent cytotoxicities against various cancer cell lines, was evaluated under several experimental conditions including addition of acids, alkalis and organic solvents. GA was stable when dissolved in acetone, acetonitrile, and chloroform, even when acids were added. However, a new derivative was produced after GA was stored in the methanol solution for a week at room temperature. The addition of alkalis could increase the rate of this chemical transformation. This derivative was determined to be gambogoic acid (GOA) by the HPLC-MS comparison with the known compound. GOA was proposed to be the product of neuclophilic addition of methanol to the olefinic bond at C-10 of GA. Furthermore, when these two compounds were tested for their cytotoxicity, GOA showed significantly weaker inhibitory effects than GA. It was therefore deduced that the alpha,beta-unsaturated carbonyl moiety at C-10 contributed to the cytotoxicity of gambogic acid.
Han
Quan-Bin
QB
Chinese Medicine Laboratory, Hong Kong Jockey Club Institute of Chinese Medicine, PR China.
Cheung
Susan
S
Tai
Joseph
J
Qiao
Chun-Feng
CF
Song
Jing-Zheng
JZ
Xu
Hong-Xi
HX
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D000432:Methanol; D012116:Resins, Plant / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D012116:Resins, Plant; D044004:Xanthones; C052659:gambogic acid; D000432:Methanol