Fluorescein hydrazones: A series of novel non-intercalative topoisomerase II alpha catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells

Abstract

Fluorescein hydrazones (5 and 7) were synthesized in three/four steps with 82-92% yields. All synthesized compounds were evaluated by topoisomerase I (topo I) and topoisomerase II alpha (topo II alpha)mediated relaxation and cell viability assays. Among them, most of the compounds showed topo I & II alpha inhibitory activity and nineteen compounds showed strong anti-proliferative activity against various cell lines. In brief, 5e inhibited 53% topo II alpha (etoposide 29%) at 20 mu M and showed excellent antiproliferative activity against DU145 (1.43 +/- 0.04 mu M), HCT15 (2.4 +/- 0.03 mu M) and MCF7 (11.4 +/- 0.5 mu M) cell lines in comparison with adriamycin, etoposide, and camptothecin. Compounds 5e, 5g and 5h were further evaluated to determine their mode of action. Compounds 5e, 5g and 5h functioned as non-intercalative topo II alpha catalytic inhibitor with induction of G1 arrest and activation of apoptotic proteins in dose dependent manner. (C) 2016 Elsevier Masson SAS. All rights reserved.