Synthesis and anticancer activity of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxins as apoptotic inducing agents

A series of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxin congeners have been synthesized. All the twenty nine compounds were evaluated for anticancer activity against five human cancer cell lines (A-549, A375, MCF-7, HT-29 and ACHN). Some of the synthesized compounds showed good anticancer activity that is comparable to etoposide. The IC50 of compounds 17a and 17f is 2.7 and 2.1 μM respectively against A-549 cancer cell line. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggested that 17a and 17f induced cell death by apoptosis.

A series of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxins have been synthesized and evaluated for their anticancer activity and apoptotic inducing ability.Figure optionsDownload as PowerPoint slideHighlights
► Twenty-nine chalcone and cinnamido-podophyllotoxins have been synthesized.
► These conjugates were evaluated for their anticancer activity.
► The active compounds 17a and 17f showed cell cycle arrest at G2/M phase.
► Hoechst staining and DNA laddering revealed that these compounds induce apoptosis.
► Caspase-3 study also suggested that these compounds induce apoptosis.