Molecular docking studies of some topoisomerase II inhibitors: Implications in designing of novel anticancer drugs

Abstract

ObjectiveThis study entails the structure-based design of type II inhibitors of human topoisomerase, by some notable anticancer compounds registered in the National Cancer Institute (NCI). The study aims to identify a series of more potent Top II inhibitors but are resistant to biochemical interaction with BRCA1 enzyme responsible for identifying and removing damaged cells resulting from a mutagenic response and finally subjecting the identified lead compound in the design of more active drug candidates. MethodsThe structure-based drug design technique employed was molecular docking and the ICM pro software was used in both the preparation of the receptor and the docking process. The results were presented in both 2-dimensional and 3-dimensional views to best capture the binding poses as well as their interaction with the amino acids present in the binding pockets. ResultsThe result of our molecular docking study showed that Rubidazone and other ligands such as DAUNORUBICIN, m-AMSA, BISANTRENE HCl and MITOXANTRONE with binding score for topoisomerase given as −32.894–2.7452, −26.231, −25.022 and −25.843 respectively, were the best topoisomerase II inhibitors. VP-16 was selected as the lead compound, which was then utilized in designing new and improving topoisomerase II inhibitors by introducing one or more secondary functional groups containing heteroatoms. ConclusionOur findings suggested that the presence of π- π, π -sigma and π-alkyl interactions of all the strategies with the receptor were primarily responsible for its firm ternary complex with topoisomerase o-DNA complex.