In silico study of synthetic Bromophenol Compounds against Staphylococcus aeurus's target protein (DHFR) Enzyme

Abstract

Natural products (NPs) serve as prototypes for a majority of antimicrobial agents currently in clinical use. The evolutionary process that gives rise to these molecules is inevitably accompanied by resistance mechanisms that curtail the clinical lifespan of any given class of antibiotics. Staphylococcus aeurus is among the class of microorganisms that exhibit resistance to multiple drugs. Dihydrofolate reductase (DHFR) enzyme is a promising target in the pursuit of mitigating S. aureus infections. This enzyme catalyzes the formation of tetrahydrofolate (THF) through the reduction of Dihydrofolate (DHF) in the presence of nicotinamide adenine dinucleotide phosphate (NADPH). Diaminopyrimidines (DAPs), such as trimethoprim (TMP), a bacterial infection treatment, which is target DHFR. DAP DHFR inhibitors have been used therapeutically for more over 30 years, and resistance to these drugs has grown prevalent. Their wide range of cellular functions make them ideal targets for antimicrobial agents. Due to the broad scope of their cellular functions, the task of developing analogues that can selectively overcome the resistance conferred by DHFR enzymes from Halopitys Incurvus Algaen's Bromophenol Compound has posed a significant challenge. To identify the compound's drug-like properties, a pre-filtering process was conducted utilizing the Lipinski rule of five in computational analysis. Subsequently, a molecular docking study was carried out using the Chimera#AutoDock Vina 1.17.3 program between the synthetic compound and DHFR (PDB ID: 2W9S) of S. aeurus and TMP was used as control. The results demonstrated that the synthetic compound displayed a favorable binding affinity with the active site of the target protein DHFR enzyme (PDB ID: 2W9S) similar to the control (TMP).