Synthesis of 1,3,6-Trioxygenated Prenylated Xanthone Derivatives as Potential Antitumor Agents

Chan      K. Lim; Lai-Yeng      Tho; Yang      M. Lim; Syed      A. A. Shah; Jean-Frederic      F. Weber

Abstract

To investigate the antitumor activities of xanthonic compounds, 10 prenylated xanthone derivatives 2-11 along with their key building block 1,3,6-trihydroxyxanthone 1 were evaluated for their potential cytotoxic activities against HeLa and MDA-MB-231 cancer cell lines. The synthesis afforded a series of prenylated derivatives with typical and new xanthone skeletons. Compounds 2, 3, 4 and 9 were reported for the first time to possess a new scaffold of 2H-xanthene- 3,9-dione. Interestingly, analogues 2 and 3 with the new scaffold demonstrated remarkable in vitro growth inhibitory activities against both the cell lines by displaying a greater cytotoxic potency than the standard drugs used in the assay, namely doxorubicin and cisplatin. In contrast, a dramatic loss of activity was observed for the O-prenylated derivatives 9- 11. These findings have highlighted the therapeutic potential of 2H-xanthene-3,9-dione scaffold to be exploitable as drug lead with specific activity against cervical and breast cancers.

Keywords: 2H-xanthene-3, 9-dione scaffold, antiproliferation, antitumor agent, cytotoxicity, synthesis, xanthone derivatives, cervical, breast cancers, cancer cell lines, O-prenylated.