Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging
concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the
keen attention of researchers to discover their therapeutic capability against cancer.
Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules
containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines.
Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c
and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT-
116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T.
Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four
cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds
4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1
phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation
of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a
correlated to its topoisomerase II inhibitory activity.
Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further
optimization to obtain promising anticancer agents.