QSAR studies on thiazole derivatives as HCV NS5A inhibitors via CoMFA and CoMSIA methods

Background: Hepatitis C Virus (HCV) infection is the major cause of hepatitis after transfusion. And HCV Nonstructural Protein 5A (NS5A) inhibitors have become a new hotspot in the study of HCV inhibitors due to their strong antiviral activity, rapid speed of viral removing and broad antiviral spectrum. Methods: Forty-five NS5A inhibitors were chosen to process three-dimensional quantitative structure-activity relationship (3D-QSAR) by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set consisting of 30 compounds was applied to establish the models and a test set consisting of 15 compounds was applied to do the external validation. Results: The CoMFA model predicted a q2 value of 0.607 and an r2 value of 0.934. And the CoMSIA model predicted a q2 value of 0.516 and an r2 value of 0.960 established on the effects of steric, electrostatic, hydrophobic and hydrogen-bond acceptor. 0.713 and 0.939 were the predictive correlation co-efficients (r2pred) of CoMFA and CoMSIA models, respectively. Conclusion: These conclusions provide a theoretical basis for drug design and screening of HCV NS5A complex inhibitors.