Design, Synthesis, and Activity Evaluation of Endogenous Hydrogen Sulfide Inhibitor of MRSA

Abstract

Eighteen indole target compounds were synthesized from 3-(6-bromo-3-indolyl)propionic acid. The chemical structures were determined by ¹H NMR, ¹³C NMR, and HRMS. Bioactivity assays revealed that 3-(6-bromo-3-indolyl)-N-(3-fluorophenyl)propenamide exhibited the most potent inhibitory effect on methicillin-resistant Staphylococcus aureus (MRSA) endogenous H₂S at a concentration of 40 μM, with an inhibitory rate of 80.2±0.92%. The results of antibacterial experiments showed that co-administering partial target compounds with oxacillin sodium reduced the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of MRSA by 50% when compared to oxacillin sodium alone. Further studies revealed that the synergistic antimicrobial mechanism is closely related to the Fenton reaction. The results of the cytotoxicity assay showed that 3-(6-bromo-3-indolyl)-N-(4-chlorobenzyl)propenamide had the least inhibitory effect on BEAS-2B cells. The experimental results of this study may provide references and ideas for the treatment of MRSA infection.