Gambogic Acid and Epigambogic Acid, C-2 Epimers with Novel Anticancer Effects from Garcinia hanburyi

Abstract

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 (IC₅₀ = 10.78 μM for K562/R and 0.66 μM for K562/S), epimers 1 and 2 exhibited similar activities against both cell lines (IC₅₀ = 1.32 and 0.89 μM for 1, IC₅₀ = 1.11 and 0.86 μM 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.

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