Abstract

Moreollic acid, a caged-tetraprenylated xanthone fromGamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation.TH12-10, with an IC50of 0.83, 1.10, and 0.79 μM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed thatTH12-10effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure–activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them,TH12-10displays the highest antitumor activities against human colon cancer cells, in which the IC50values in DLD1 and SW620 are lower than that of 5-fluorouracil.Keywords:Gamboge;structural optimization;synthesis;antitumor