Abstract

3D QSAR STUDIES ON THIAZOLIDINONE DERIVATIVES AS POTENTIAL EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITORS

Sanmati K Jain*, Ravi Tripathi and Piyush Ghode

Abstract

Three dimensional quantitative structure activity relationship (3D QSAR) analysis was performed on thiazolidinone analogues for their Epidermal Growth Factor inhibitory activity (EGFR inhibitors) by k Nearest Neighbor Molecular Field Analysis (kNN-MFA) method using Molecular Design Suite (VLife MDS) software. kNN-MFA coupled with stepwise variable selection (forward-backward) method was applied to derive QSAR models and these models were validated for statistical significance by internal and external validation. Among the models generated, two models with optimum values of validation parameters had q2 and predr2 values of 0.8032 and 0.7843 for model 1 and 0.7933 and 0.7700 for model 2 respectively. The negative value of steric field point at S_374 in both the models indicates the need of less bulky group at this point for favorable biological activity. The positive value of electrostatic field point at E_555 suggests the need of positive ionizable group. The present work may help in providing guidance for further lead optimization and designing of potent anticancer agents.

Keywords: 4-Thiazolidinone, EGFR, QSAR, anticancer.