Design, synthesis and biological evaluation of 1, 3-diphenylbenzo[f][1, 7]naphthyrdines. Issue 20 (15th October 2017)

• Record Type: Journal Article
• Authors: Arepalli, Sateesh Kumar; Park, Byeongwoo; Lee, Kiho; Jo, Hyunji; Jun, Kyu-Yeon; Kwon, Youngjoo; Kang, Jong-Soon; Jung, Jae-Kyung; Lee, Heesoon
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 20(2017)
• Page Start: 5586
• Page End: 5597
• Publication Date: 2017-10-15
• Subjects: 1, 3-Diphenylbenzo[f][1, 7]benzonaphthyrdines -- Human Topoisomerase IIα inhibitors -- Cytotoxic agents -- Molecular docking studies -- Imino Diels-Alder reaction; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.08.030
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Novel benzo[ f ][1, 7]naphthyrdines were designed and synthesized. One-pot, atom-economy, regio-selective and multi-component reaction. Half of the compounds exhibited significant in vitro cytotoxic activities. The compound4l displayed excellent human Topo IIα inhibition than the etoposide. 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 them4l, 4m, and4o derivatives exhibited most promising cytotoxic activities. Furthermore these compounds were evaluated against human Topoisomerase IIα inhibition. Interestingly, the compound4l exhibited 1.3 and 1.2 times more potent human Topoisomerase IIα inhibition than the reference drug etoposide in both 100 µM and 20 µM concentrations respectively. Molecular docking studies for the compound4 l have also been executed by Sybyl X-2.1 in which it reveals the binding site of the compound4l with topo IIα DNA cleavage site where etoposide was situated. The benzo[ f ][1, 7]naphthyridine ring was stacked between the DNA bases of the cleavage site.