Microwave synthesis of novel halogenated β-enaminonitriles linked 9-bromo-1H-benzo[f]chromene moieties: Induces cell cycle arrest and apoptosis in human cancer cells via dual inhibition of topoisomerase I and II

Abstract

A novel series of halogenated β-enaminonitriles (4a-m), linked 9-bromo-1H-benzo[f]-hromene moieties, were synthesized via microwave irradiation and were predestined for their cytotoxic activity versus three cancer cell lines, namely: MCF-7, HCT-116, and HepG-2. Several of the tested compounds showed high growth inhibitory activities versus the tumor cell lines. Particularly, compounds 4c, 4d, 4f, 4h, 4j, 4l, and 4m demonstrated superior antitumor activities against the aforementioned cell lines. Moreover, the apoptosis process in all the tested cells was induced by compounds 4c, 4d, 4h, 4l, and 4m, as observed by the Annexin V/PI double staining flow cytometric assay. The DNA flow, cytometric analysis revealed that these compounds prompted cell cycle arrest at the G2/M phases. Furthermore, the topoisomerase catalytic activity assays indicated that these compounds inhibited both the topoisomerase I and II enzymes.

Keywords: Antitumor activity; Benzochromenes; Cell cycle analysis; Microwave synthesis; SAR study; Topoisomerase.