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QSAR Studies on Thiazole Derivatives as HCV NS5A Inhibitors via CoMFA and CoMSIA Methods

[ Vol. 16 , Issue. 4 ]

Author(s):

Jiayu Li, Wenyue Tian, Diaohui Gao, Yuying Li, Yiqun Chang, Jun Xu, Junxia Zheng* and Pinghua Sun*   Pages 453 - 460 ( 8 )

Abstract:


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.

Keywords:

3D-QSAR, thiazole derivatives, HCV, NS5A inhibitors, broad antiviral spectrum, strong antiviral activity.

Affiliation:

Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632

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