Quantitative structure-activity relationship and molecular docking studies of some series of imidazole derivatives as anti-hepatitis C drug

Abstract

Hepatitis C virus (HCV) NS5B RNA-depended-RNA-polymerase (RdRp) is an essential enzyme in HCV viral replication and has no functional equivalent in mammalian cells. In silico study was carried out to develop a Quantitative structure activity-relationship and molecular docking on some selected imidazole derivatives as anti-hepatitis C compounds. Density functional theory with B3LYP/6-311G* was employed for complete geometry optimization Five QSAR models were generated using Genetic Function Algorithm (GFA) of the material studio software version 8, in which model one (1) was selected as the best model and reported based on the validation parameter with the squared correlation coefficient (R²) of 0.7114. Adjusted squared correlation coefficient (R² adj) value 0f 0.6458 and cross-validation coefficient (Q²) LOO 0.5810. The best model that is model (1) was subjected to external validation and was found to be R² pred. = 0.5729. The result obtained from molecular docking studies shows that the compound with the best binding affinity of -10.7 Kcal/mol formed hydrogen bonding of (GLN 446 and GLU143) and hydrophobic interaction with the amino acid residues of  the Non-Structural 5B polymerase(NS5B polymerase) receptor. The QSAR model and molecular docking results propose the direction of designing new imidazole derivatives agent with better activity against the NS5B polymerase target site.

Keywords: Binding affinity, HCV, imidazole, molecular docking, NS5B polymerase, QSAR