Computational techniques in designing a series of 1,3,4-trisubstituted pyrazoles as unique hepatitis C virus entry inhibitors

Abstract

In this study, we developed a QSAR model for studying the antiviral activity of 1,3,4-trisubstituted pyrazoles derivatives on hepatitis C virus infected in human HuH-7 cell lines. We employed random analysis to split the data sets. Statistically robust model was generated with R2, Q2 and R2pred values of 0.777, 0.731 and 0.774 respectively. The reliability of this model was confirmed by acceptable validation parameters, and this model also fulfilled the Golbraikh and Tropsha standard model conditions. Through the evaluation of selected molecular descriptors we observed that, topological charge index of order 4 (GGI4), mean topological charge index of order 1 (JGI1), octanol water partition coefficient (XlogP), 3D topological distance based autocorrelation lag5/weighted by polarizabilities (TDB5p) and total molecular surface area (FPSA-2) are the molecular properties determining biological activities of the study compounds, which shed light on the vital features that aid in the design of unique potent hepatitis C virus entry inhibitors using computer-aided drug design tools.