Abstract

2D & 3D QSAR AND DRUG DESIGNING OF PHENOTHIAZINE DERIVATIVES AS POTENT ANTITUBERCULAR AGENTS

Priyadarshini Agarwal*

Abstract

In search of newer and potent antitubercular agents, a series of phenothiazine derivatives were subjected to 2D and 3D quantitative structure-activity relationship (QSAR) analyses. Statistically significant models were generated, and the most robust model for 2D QSAR was obtained using partial least square regression method coupled with stepwise forward-backward method using V-Life Molecular Design Suite software version 3.5. The physicochemical descriptors, viz., slogp, estate descriptors like Saa CHE index and Chiv2, contribute significantly to the biological activity. About 20 QSAR models were generated, among which 2 significant models were finally selected on the basis of various statistical parameters such as squared correlation coefficient (r2), and cross-validated square correlation co-efficient (q2). The statistical values of the 2 significant models (model 1, model 2) are r2(0.9444, 0.9437) and q2(0.8454, 0.8374). The descriptors showed by QSAR study can be used further for study and designing of new compounds. Consequently, this study may prove to be helpful in development and optimization of existing antitubercular activity of this class of compounds.

Keywords: Antitubercular, Mycobacterium tuberculosis, Partial Least Square, Phenothiazine Derivatives, QSAR, Type II NADH.