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.

Novel halogenated β -enaminonitriles linked 9-bromo-1 H -benzo f -chromene moieties with dual inhibition of Topoisomerase I and II. • 4 H -Benzo h chromenes were synthesized as potential anticancer agents. • The cytotoxic activity was tested against MCF-7, HCT-116 and HepG-2 cell lines. • Compounds 4c,d,h,l,m were induce cell cycle arrest at G2/M phase. • Compounds 4c,d,h,l,m prompting apoptotic cell death due to the dual inhibitory effect on the catalytic activity of topoisomerase I and II. A novel series of halogenated β -enaminonitriles (4a-m), linked 9-bromo-1 H -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. [ABSTRACT FROM AUTHOR]