Ultrasound Assisted-synthesis and Biological Evaluation of Piperazinylprop- 1-en-2-yloxy-2H-chromen-2-ones as Cytotoxic Agents

Publisher： Bentham Science Publishers

E-ISSN： 1875-628x|14|10|1195-1205

ISSN： 1570-1808

Source： Letters in Drug Design & Discovery, Vol.14, Iss.10, 2017-09, pp. : 1195-1205

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Background: The molecular hybridization concept was used to develop novel coupledderivatives with the hope of synergistic cytotoxic activity. A novel class of 12 derivatives, containingcoupled 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 apanel of three human cancer cell lines viz MCF-7 (human breast cancer cell line), HeLa (humancervical cancer cell line), NCI-H226 (non-small cell lung cancer cell line). Most of the compoundsexhibited promising cytotoxicity; some compounds have shown GI50 values similar to that of thestandard drug, Adriamycin. Compounds 4d, 4b, and 4a were found to be the most promising cytotoxicderivatives in this study.

Results: Molecular docking study was performed to support the effective binding of compounds atthe active site of the enzyme and to know the binding mode of synthesized compounds for inhibitionof topoisomarase II. Further, the compounds docking results against topoisomerase-II were ingood agreement with the observed GI50 values.

Conclusion: A computational study was performed for prediction of ADME properties and it wasobserved that the compounds exhibited good % absorption; all the tested compounds 4(a-l) followedthe criteria for an orally active drug and, therefore, these compounds can have a good potentialfor eventual development as oral agents.