Gambogic acid and epigambogic acid, C-2 epimers with novel anticancer effects from Garcinia hanburyi.
Gambogic acid, usually isolated as an inseparable stereomeric mixture of C-2 epimers, was newly separated into two epimers (1 and 2) from the gamboges of Garcinia hanburyi. The stereochemistry at C-2 was clearly defined by extensive spectroscopic analysis and direct comparison of NMR and HPLC data with those of the known R-epimer. Both epimers were examined for their cytotoxicities against human leukemia K562 (K562/S) and doxorubicin-resistant K562 (K562/R) cell lines. Different from doxorubicin (IC (50) = 10.78 microM for K562/R and 0.66 microM for K562/S), epimers 1 and 2 exhibited similar activities against both cell lines (IC(50) = 1.32 and 0.89 microM for 1, IC(50) = 1.11 and 0.86 microM for 2). These results suggested that both epimers were not multidrug resistance (MDR) substrates. Furthermore, epimers 1 and 2 were tested for their inhibitory effects against six human cytochrome P-450 enzymes. Epimers 1 and 2 showed little inhibitory effects toward five of the enzymes except CYP2C9. Interestingly, when tested against CYP2C9, S-epimer 2 had an inhibitory effect 20-fold stronger than that of R-epimer 1.
Han
Quanbin
Q
Chinese Medicine Laboratory, Hong Kong Jockey Club Institute of Chinese Medicine, Shatin, NT, PR China.
Yang
Ling
L
Liu
Yong
Y
Wang
Yulin
Y
Qiao
Chunfeng
C
Song
Jingzheng
J
Xu
Lijia
L
Yang
Dajian
D
Chen
Shilin
S
Xu
Hongxi
H
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D029760:Garcinia; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D044004:Xanthones; C052659:gambogic acid