Studies on chemical modification and biology of a natural product, gambogic acid (III): determination of the essential pharmacophore for biological activity.

Research paper by Xiaojian X Wang, Na N Lu, Qian Q Yang, Dandan D Gong, Changjun C Lin, Shenglie S Zhang, Meiyang M Xi, Yuan Y Gao, Libing L Wei, Qinglong Q Guo, Qidong Q You

Indexed on: 22 Feb '11Published on: 22 Feb '11Published in: European Journal of Medicinal Chemistry


Caged 4-oxa-tricyclo[,7)]dec-2-one structural motifs are found in Garcinia natural products that demonstrate anti-tumor activity. Gambogic acid (GA, 1), the most abundant caged Garcinia xanthones, has been reported to be a promising anti-cancer agent. To identify the essential pharmacophore for its anti-tumor activity, a series of GA analogues that address potential key structural features for biological activity were synthesized, among which compound 11a displayed comparable in vitro anti-tumor activity as GA. Mechanistic studies on 11a determined that the compound induces apoptosis as well as arrests the G2/M phase of the cell cycle in HepG2 cells. The determination of the essential part of the scaffold found in GA to maintain anti-tumor effects, and the SAR based on the caged pharmacophore are reported and will provide key information for future anti-cancer drug development studies.