An array of chalcones from vanillin/isovanillin and differently substituted acetophenones were synthesized and assessed for their anticancer activity against A549, MCF7 and MIA PaCa-2 cell lines using MTT assay. Some of the chalcones exhibited good anticancer activity with IC 50 values below 10 lM. Compound 5f with IC 50 values 5.4 ± 0.7, 10.45 ± 2.15 and 13.0 ± 1.68 lM on MIA PaCa-2, A549 and MCF7, respectively, was more potent than curcumin and hence was analyzed for changes in cell morphology, inhibition of cell migration, mechanism of cell death and arrest of cell cycle progression on MIA PaCa-2 cells.