Akademik Veri Yönetim Sistemi
Journal of the Turkish Chemical Society, Section A: Chemistry, cilt.6, sa.1, ss.71-78, 2019 (Scopus)
© 2019, Turkish Chemical Society. All rights reserved.DNA topoisomerases are proved therapeutic targets of antibacterial and anticancer drugs. Structures of topoisomerase-DNA and inhibitor ternary complexes have revealed the exact binding sites and mechanisms of topoisomerase poisons. There are two isoforms of Human Topoisomerase II; α and β. Both of them perform similar functions and their levels differ depending on the replicative activity and type of tissue. Topo IIα is preferentially expressed in proliferating cells. Thus, selective Topo IIα inhibitors have been of particular interest in cancer therapy, as they may represent a more targeted approach to highly proliferative cells. In this study, we use structure-based virtual screening method with molecules which are commercially available in the ZINC database. Docking studies were performed by Glide module available in Schrödinger software, to obtain an efficient collection of hit molecules ligand filtration was also done by employing Lipinski’s “rule of five” and pharmacokinetic properties were tested using Qikprop module. From approximately ten thousand compounds from Zinc database we selected 4 top chemical structures with suitable ADME/Tox properties and good inhibiting profile for topo II. Thus compounds 1-4 could be the promising inhibitors of human topo IIα enzyme.