Synthesis and Evaluation of Gamgogic Acid Analogs as Cytotoxic Agents
Gambogic acid (1, GA) was isolated from the resin of Garcinia hanburyi Hook. f. (Clusiaceae), a tree growing in Southeast Asia. The resin is used in folk medicine and as coloring agent in China (1,2). The chemical structure of GA shows a unique 4-oxatricyclo[18.104.22.168]decan-2-one ring system attached to a xanthone backbone.3 In order to analyze structure-activity relationships (SAR) of GA, we converted it into xanthonic derivatives (Figure 1) and performed the synthesis of some structurally related prenylated derivatives, using as building blocks 1,3,6-trihydroxyxanthone (2) and tested them for cytotoxic activity. All newly synthesized compounds were assayed for in vitro cytotoxicity against 4 human cancer cell lines: KB (nasopharyngeal), KBvin (multidrug-resistant nasopharyngeal over-expressing P-gp), A549 (lung) and DU-145 (prostate). Among them, compounds 9 and 10 showed remarkable IC50 values of 0.91 and 0.82µg/mL, respectively, against KBvin cells.
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