Planta Med 2011; 77 - PG21
DOI: 10.1055/s-0031-1282505

Synthesis and Evaluation of Gamgogic Acid Analogs as Cytotoxic Agents

C Yen 1, N Kyoko 2, FB Kenneth 3, Y Wu 4, K Lee 2
  • 1Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
  • 2Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599–7568, USA
  • 3Division of Medicinal Chemistry and Natural Products, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599–7568, USA
  • 4Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Natural Medicinal Products Research Center, China Medical University Hospital, Taichung 40402, Taiwan.

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[]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.

Figure 1: The structures of compounds 9 and 10

References: 1. Ollis WD, Redman BT, Sutherland IO, Jewers K (1969)J Chem Soc Chem Commu. 15: 879–880.

2. Kumar P, Baslas RK (1980) Herba Hung 19: 81–91.

3. Li NG et al. (2007) Chin Chem Lett 18: 659–662.