CoMFA vs. Topomer CoMFA, which One is better a Case Study with 5-Lipoxygenase Inhibitors

Abstract

AbstractQuantitative structure-activity relationships (QSAR) have been applied for two decades in the development ofrelationships between physicochemical properties of chemical substances and their biological activities to obtain a reliablestatistical model for prediction of the activities of new chemical entities. The fundamental principle underlying the QSARis that the structural difference is responsible for the variations in biological activities of the compounds. In this work,we developed 3D-QSAR model for a series of 5-Lipoxygenase inhibitors, utilizing comparative molecular field analysis(CoMFA) and Topomer CoMFA methodologies. Our developed models addressed superiority of Topomer CoMFA overCoMFA. The CoMFA model was obtained with q 2 =0.593, r=0.939, Q=0.334 with 6 optimum number of components(ONC). Higher statistical results were obtained with the Topomer CoMFA model (q 2 =0.819, r 2 =0.947, ONC=5). Furtherrobustness of developed models was checked with the ANOVA test and it shows F=113 for CoMFA and F=162.4 forTopomer CoMFA model. Contour map analysis indicated that the more requirement of electrostatic parameter for improvedpotency. Key words: CoMFA, Topomer CoMFA, 5-Lipoxygenase, 3D-QSAR