Molecular modeling studies on DNA topoisomerase I inhibitors
Ilkay Yildiz, Sanaz Ataei, Esin Karatas, Egemen Foto and Nuran Diril
Ankara University, Turkey
Hacettepe University, Turkey
: J Pharm Drug Deliv
Abstract
DNA topoisomerases, which catalyze the interconversion of various topological states of DNA, were originally discovered to change the superhelical structure of closed circular DNAs. Depending on the nature of the reactants and reaction conditions, topoisomerases can catalyze DNA relaxation/supercoiling, catenation/decatenation and knotting/unknotting reactions. Based on their functional mechanisms, DNA topoisomerases have been classified into two types. Type I DNA topoisomerase breaks and rejoins only one of the two strands during catalysis, while type II DNA topoisomerase acts on both strands for each DNA strand-passing reaction and it requires ATP for full activity. The mechanisms of intereference with Topoisomerase activity are quite different and can be divided into two classes; Topoisomerase poisons and Topoisomerase catalytic inhibitors. Investigation of the inhibitory activity of eukaryotic Topoisomerases is widely used in anticancer drug development. In this study, molecular modeling studies such as pharmacophore analysis and molecular docking were realised using software Discovery Studio 3.5, because of the lead optimisation and generation of DNA Topoisomerase I inhibitory active heterocyclic compounds and the results were discussed.
Biography
Email: Ilkay.Yildiz@pharmacy.ankara.edu.tr
