Design, synthesis, and biological and docking studies of novel epipodophyllotoxin-chalcone hybrids as potential anticancer agents

A series of new compounds consisting of epipodophyllotoxin-chalcone hybrids was synthesized towards the development of better anticancer lead molecules. These hybrids consist of structurally different but functionally similar topoisomerase-II inhibitors which were conjugated together through click-chemistry. Their design is aimed at the synthesis of novel chemotherapeutics with a better target-protein interaction and higher bioavailability. Evaluation of the anticancer activity of these designed conjugates against a panel of six human cancer cell lines proved their potential cytotoxicity. Further, these compounds were docked against topoisomerase-II and the energy calculations were in good agreement with the observed IC50 values. Compounds 6d, 6f, 7d and 7f exhibited significant in vitro cytotoxicity. Among all the compounds evaluated, compound 7f was found to be the most promising, especially selective against SW-620 and SKN-SH cell lines.