Quantitative structure activity relationship studies of topoisomerase i inhibitors as potent antibreast cancer agents

Abstract

Topoisomerase I (TOP I) is a valuable molecular target for the development of clinically used anticancer agents. Indenoisoquinolines have emerged as potent topoisomerase I inhibitors. So, with an aim to elucidate the important features responsible for their activity, QSAR studies on breast cancer cell line using stepwise multiple linear regressions, partial least square, and neural network were performed. The MLR and PLS models showed good correlation values of r2=0.932, r2cv=0.897, and r2=0.932, r2cv=0.913 respectively. The model revealed the importance of steric arrangement of functional groups and number of H bond acceptors. In addition to MLR and PLS, neural network architecture was also constructed using selected descriptors and the inhibitory activities in order to evaluate the mode of dependencies of biological activity on obtained descriptors. © 2013 Supriya Singh et al.