Background: The molecular hybridization concept was used to develop novel coupled
derivatives with the hope of synergistic cytotoxic activity. A novel class of 12 derivatives, containing
coupled 7-oxycoumarin, piperazine, and heteryl/ aryl propenone moieties namely, 4-methyl-7-
(3-(4-methylpiperazin-1-yl)-3-oxo-1-substituted phenyl/heteryl prop-1-en-2-yloxy)-2h-chromen-2-
ones were synthesized by an ultrasound-assisted, eco-friendly protocol.
Methods: All the designed hybrids were evaluated for their in vitro cytotoxic activity against a
panel of three human cancer cell lines viz MCF-7 (human breast cancer cell line), HeLa (human
cervical cancer cell line), NCI-H226 (non-small cell lung cancer cell line). Most of the compounds
exhibited promising cytotoxicity; some compounds have shown GI50 values similar to that of the
standard drug, Adriamycin. Compounds 4d, 4b, and 4a were found to be the most promising cytotoxic
derivatives in this study.
Results: Molecular docking study was performed to support the effective binding of compounds at
the active site of the enzyme and to know the binding mode of synthesized compounds for inhibition
of topoisomarase II. Further, the compounds docking results against topoisomerase-II were in
good agreement with the observed GI50 values.
Conclusion: A computational study was performed for prediction of ADME properties and it was
observed that the compounds exhibited good % absorption; all the tested compounds 4(a-l) followed
the criteria for an orally active drug and, therefore, these compounds can have a good potential
for eventual development as oral agents.