Pharmacophore an International Research Journal
Topoisomerase is an essential enzyme required for DNA replication and hence playing a pivotal role in oncology. Known and validated target in anticancer drug discovery, and the well-established link between the higher enzyme activity and malignancy, makes topoisomerase an excellent target. In this study, a series of 36 topoisomerase I and II dual inhibitors, having indolizino[6,7-b]indole ring system as the core scaffold, was subjected to molecular modelling study. Molecular attributes such as steric, electrostatic and hydrogen bonding and their effect on biological activity were established using 3D QSAR tools; comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Dual inhibition and indole ring may make these molecules potential anticancer agents. Robust and statistically sound model was derived having significant r2 and r2pred values giving better understanding of crucial regions around the scaffold to afford better activity. Dividing the series into test and training sets allowed calculations validating the predictive ability of the model. The contour maps and statistical analyses may provide positive assistance in developing similar molecules in future.
