7-O-aminoalkyl-2,3-dehydrosilibinins: Synthesis and in vitro Anti-cancer Efficacy

Abstract

A series of 7-O-aminoalkyl-2,3-dehydrosilibinin derivatives were synthesized and evaluated for their antiproliferative activities against several cancer cell lines. A number of them exhibited greatly enhanced potency with 50% growth inhibition at low micromolar concentrations. Structure activity study indicated that the distance between N and 7-O on the side chain has a limited influence on the antiproliferative activity, while the presence of a morpholino group decreases the antiproliferative activities dramatically. Flow cytometry based assays on human colon cancer HCT116 cells revealed that 6a and 6c, two of the most potent derivatives, effectively arrest the cell cycle in the G2 phase and stimulate cell apoptosis. Our findings suggest that attaching an appropriate tertiary amino alkyl side chain through 7-O-alkylation on 2,3-dehydrosilibinin, would be a viable strategy for the development of silibinin derivatives as anticancer agents.