TY  - JOUR
T1  - Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method
AU  - Ertan-bolelli, Tugba
AU  - Bolelli, Kayhan
PY  - 2019
DA  - May
Y2  - 2019
DO  - 10.18596/jotcsa.466457
JF  - Journal of the Turkish Chemical Society Section A: Chemistry
JO  - JOTCSA
PB  - Turkish Chemical Society
WT  - DergiPark
SN  - 2149-0120
SP  - 71
EP  - 78
VL  - 6
IS  - 1
LA  - en
AB  - DNAtopoisomerases are proved therapeutic targets of anticancer and antibacterialdrugs. Structures oftopoisomerase–DNA and inhibitor ternary complexes have revealed the exactbinding sites and mechanisms of topoisomerase poisons. There are two isoformsof Human Topoisomerase II; α and β. Both of them perform similar functions andtheir levels differ depending on the replicative activity and type of tissue.Topo IIα is preferentially expressed in proliferating cells. Thus selectiveTopo IIα inhibitors have been of particular interest in cancer therapy, as theymay represent a more targeted approach to highly proliferative cells.In thisstudy, we use structure based virtual screening method with molecules which arecommercially available in the ZINC database. Docking studies were performed byGlide module available in Schrödinger software, Ligand filtration was also doneto obtain an efficient collection of hit molecules by employing Lipinski “ruleof five” and pharmacokinetic properties of the compounds were tested usingQikprop module. From approximately ten thousand compounds from Zinc databaseit was possible to select 4 top chemical structures with good inhibitingprofile for topo II, with suitable ADME/Tox properties, thus comp. 1-4 could bethe promising inhibitors of human topo IIα enzyme.
KW  - anticancer activity
KW  - docking
KW  - topoisomerase
KW  - virtual screening
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UR  - https://doi.org/10.18596/jotcsa.466457
L1  - https://dergipark.org.tr/en/download/article-file/641993
ER  -