High-Throughput Virtual Screening of Compounds with Electrophilic Fragments for New Potential Covalent Inhibitors of Bacterial Proteins

Abstract

Abstract: Search for new antibacterial drugs has continued to be an urgent request. One of the approaches is development of covalent inhibitors using biochemoinformatics at initial stages. In this work, structures of few plant-derived substances with electrophilic unsaturated carbonyl & structures of small synthetic compounds suitable for fragment-based drug discovery (FBDD) with - CH2-Br group were selected as ligands for sets of structures of bacterial proteins. Theoretical assessment was carried out using the Autodock Vina program for calculation and FYTdock for organization the process and analysis of results. Natural Ixerine D as well as synthetic 4-(4-(2- bromoethyl)piperazin-1-yl)-7-nitrobenzofurazan demonstrated the most promising results as potential Cys-targeted inhibitors.