Ligand-based Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies for Discovery of Potential Topoisomerase I Inhibitors.

ABSTRACT: Camptothecin (CPT), a natural product and its synthetic derivatives exert potent anticancer activity by selectively targeting DNA Topoisomerase I (Top1) enzyme. CPT and its clinically approved derivatives are used as Top1 poisons for cancer therapy suffer from many limitations related to stability and toxicity. In order to envisage structurally diverse novel chemical entity as Top1 poison with better efficacy, Ligand-based-pharmacophore model was developed using 3D QSAR pharmacophore generation (HypoGen algorithm) methodology in Discovery studio 4.1 clients. The chemical features of 29 CPT derivatives were taken as the training set. The selected pharmacophore model Hypo1 was further validated by 33 test set molecules and used as a query model for further screening of 1,087,724 drug-

SUBMITTER: Pal S 

PROVIDER: S-EPMC6396084 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature