Marine Streptomyces-derived Antibacterial Compound [2, 4-Dichloro-5-sulfamoyl benzoic acid] for MRSA and VRE Strains

Abstract

The aim of the present study was to predict the interaction of 4-dichloro-5-sulfamoyl benzoic acid (DSBA) derived from Streptomyces sp. VITBRK3 with the drug target enzymes of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococci (VRE) strains procured from ATCC. Two proteins dihydropteroate synthetase (DPS) and dihydrofolate reductase (DFR) were chosen as drug targets. The well-known folic acid synthesis inhibitor amino salicylic acid (ASA) was taken as a positive control. AutoDock 4.2.1 was used to perform the protein-ligand docking analysis. DSBA showed least binding energy of –6.99 kcal/mol and inhibition constant of 7.5 µM and formed 8 hydrogen bonds with DFR. DSBA showed least binding energy of -5.6 kcal/mol and inhibition constant of 78.58 µM and formed 7 hydrogen bonds with DPS.  ASA showed the binding energy of –4.97 kcal/mol, and inhibition constant of 225.9 µM and formed 5 hydrogen bonds with DPS protein. It showed the binding energy of          –4.68 kcal/mol, and inhibition constant of 371.32 µM and formed 4 hydrogen bonds with DFR protein. DSBA has qualified CMC rule, lead like rule and Lipinski’s rule of five. The compound DSBA does not possess any carcinogenic effect in rat or mouse model. Osiris Property Explorer analysis suggested that, DSBA does not possess any major side effects and is a suitable drug candidate. Pre ADMET analysis also suggests that, the lead compound, DSBA is a suitable drug candidate. The results of this study suggest that the antimicrobial activity of DSBA against MRSA and VRE strains is due to its inhibition over bacterial cell wall folic acid biosynthesis.