Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of thiazolone derivatives as hepatitis C virus NS5B polymerase allosteric inhibitors.

Journal of Computer-aided Molecular Design
Beilei LeiXiaojun Yao

Abstract

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models for a series of thiazolone derivatives as novel inhibitors bound to the allosteric site of hepatitis C virus (HCV) NS5B polymerase were developed based on CoMFA and CoMSIA analyses. Two different conformations of the template molecule and the combinations of different CoMSIA field/fields were considered to build predictive CoMFA and CoMSIA models. The CoMFA and CoMSIA models with best predictive ability were obtained by the use of the template conformation from X-ray crystal structures. The best CoMFA and CoMSIA models gave q (2) values of 0.621 and 0.685, and r (2) values of 0.950 and 0.940, respectively for the 51 compounds in the training set. The predictive ability of the two models was also validated by using a test set of 16 compounds which gave r (pred) (2) values of 0.685 and 0.822, respectively. The information obtained from the CoMFA and CoMSIA 3D contour maps enables the interpretation of their structure-activity relationship and was also used to the design of several new inhibitors with improved activity.

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Citations

Jun 29, 2011·Future Medicinal Chemistry·Maria Letizia BarrecaVioletta Cecchetti
Mar 19, 2014·Ecotoxicology and Environmental Safety·M Salahinejad, J B Ghasemi
Jun 9, 2015·Journal of Receptor and Signal Transduction Research·Bharathkumar InturiMadhusudhan N Purohit
Oct 12, 2010·Molecular Diversity·Eslam PourbasheerParviz Norouzi
Dec 7, 2011·Journal of Chemical Information and Modeling·Kuei-Chung ShihNai-Wan Hsiao
Dec 25, 2010·Journal of Chemical Information and Modeling·Kuei-Chung ShihChuan-Yi Tang

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