Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase II alpha catalytic inhibitor

Abstract

For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2- or 4- phenyl ring displayed selective and significant topoisomerase II alpha (topo II alpha) inhibitory activity and potent antiproliferative activity. Positive correlation between topo II alpha inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalative topo Ha catalytic inhibitor. (C) 2014 Elsevier Masson SAS. All rights reserved.