Docking Studies of Triazole Compounds as Potential Inhibitors of Decaprenylphosphoryl-D-ribose 2′-Epimerase: Towards Novel Therapeutic Strategies for Mycobacterial Diseases

Abstract

A series of novel triazole derivatives were designed to target the Decaprenylphosphoryl-D-ribose 2′-epimerase (DprE1) enzyme by combined ligand and structure-based approach. The designed molecules were then further subjected to molecular docking simulations. Out of 32 designed compounds, the simulations helped to identify critical binding residues as well as probable hydrogen bonding and hydrophobic interactions, providing insight into the ligand-binding mechanism towards DprE1 inhibitors. As far as antitubercular activity, five designed compounds shown docking scores for oxidoreductase were 7.6, -6.6, -7.3, and -7.2 for compounds 1B, 3D, 5D, 6B, and 6C, respectively, indicating excellent binding affinity. This work helps the rational design and optimization of drugs targeting DprE1 for possible anti-tubercular uses by revealing the binding mechanisms and affinities. The discovered interaction patterns serve as a roadmap for further experimental exploration and the advancement of potent DprE1 inhibitors. Therefore, the interactions between DprE1 and new triazole derivatives have been thoroughly investigated through this computational study.