Design, synthesis, and anticancer evaluation of novel andrographolide derivatives bearing an α,β-unsaturated ketone moiety.

Abstract A series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory activities against both HCT116 and MCF-7 cell lines, with IC50 values of 2.49 and 7.80 μM respectively. Preliminary anticancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 10b against HCT116 using flow cytometry, and the results indicated that 10b blocked the proliferation of HCT116 cells by inducing cell apoptosis in a concentration-dependent manner and arresting cell cycle in G2/M phase.