Design, synthesis and biological evaluation of 1,3-diphenylbenzo[f] [1,7]naphthyrdines

Abstract

A novel series of twenty 1,3-diphenylbenzo[f][1,7]benzonaphthyrdine derivatives were designed and synthesized through intermolecular imino Diels-Alder reaction. Their in vitro cytotoxic activities were evaluated against six human cancer cell lines (NCIH23, HCT15, NUGC-3, ACHN, PC-3, and MDA-MB-231). Majority of synthesized compounds exhibited significant cytotoxic activities against all tested human cancer cell lines. Among them 4l, 4m, and 4o derivatives exhibited most promising cytotoxic activities. Furthermore these compounds were evaluated against human Topoisomerase II alpha inhibition. Interestingly, the compound 4l exhibited 1.3 and 1.2 times more potent human Topoisomerase II alpha inhibition than the reference drug etoposide in both 100 mu M and 20 mu M concentrations respectively. Molecular docking studies for the compound 4l have also been executed by Sybyl X-2.1 in which it reveals the binding site of the compound 4l with topo II alpha DNA cleavage site where etoposide was situated. The benzo[f][1,7]naphthyridine ring was stacked between the DNA bases of the cleavage site. (C) 2017 Elsevier Ltd. All rights reserved.