Topoisomerase is a critical enzyme vital for DNA replication and consequently playing a pivotal role in oncology. Being a validated target in anticancer drug discovery and having a well-established link between the higher enzyme activity and malignancy, topoisomerase has become an excellent target to inhibit. In this study, a series of 21 topoisomerase I inhibitors, having Indenoisoquinoline ring system as the parent scaffold, was taken for molecular modeling. Molecular characteristics such as steric, electrostatic and hydrogen bonding and their influence on afforded biological activity were established using 3D QSAR techniques; comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Top1 inhibition and indenoisoquinoline ring may make these molecules potential molecules in oncology. A statistically comprehensive and robust model was developed having significant r2 and r2pred values giving better insights of spatially focal regions around the scaffold which directly have an effect on the degree of biological activity. Segregating the series into test and training sets allowed calculations authenticating the predictive ability of the developed model. Coloured contour maps and statistical analyses might provide substantial assistance in developing better molecules with similar structures in future.
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