Molecular modeling and docking analysis of bis-indolymethanes derivatives as human β-glucuronidase enzyme inhibitors

Abstract

β-glucuronidase enzyme is present mostly in mammals’ tissues. β-glucuronidase is present in kidney, bile, serum, urine and spleen. In eukaryotic and prokaryotic organisms, it is important in the process of breaking down of β-glucuronide. It also helps in the neutralization of reactivity of some metabolites that are associated to many diseases. The most stable geometry of the dataset were obtained adopting DFT method at B3LYP/6-31G* level of theory. The model was developed using MLR analysis adopting GFA method. Molecular docking was also performed to portray the binding mode of these bis-indolymethanes derivatives in the binding pocket of their target receptor (human β-glucuronidase). The selected model was assessed and chosen based on its statistical fitness with R²_trng=0.907233, R²_adj=0.881465,  Q_cv²=0.833795, and R²_test=0.609841. And also, the significance and impart of each physicochemical parameters to the selected model were determine by their ME values. Molecular docking analysis revealed that amino acid such as ALA49, SER52, ASP53, PHE51, VAL96, LEU92, TYR188, TYR199 and PHE200 might be responsible for the most promised binding affinity of the reported docked ligands. The molecular docking results showed that the reported compounds were better than the standard β-glucuronidase inhibitor. The results of this findings paved way for designing novel β-lucuronidase inhibitors.