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

A series of 4 beta-alkylamidochalcone and 4 beta-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 mu M 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. (C) 2011 Elsevier Masson SAS. All rights reserved.