The incidence of treatment failure due to multidrug-resistant pathogens elevated over the years; the rate is much higher than new antibiotic drug discovery. Therefore, bromophenol derivatives as potential antibacterial agents on Staphylococcus aureus and MRSA were explored in this research via integrating chemistry, microbiology, and pharmacology to address significant knowledge gaps pertaining to the antibacterial activity of bromophenols based on their functional groups. Surprisingly, a simple molecule, 3-bromo-2,6-dihydroxyacetophenone (2), exhibited good anti-S. aureus activity and even MRSA, a drug-resistant strain. In addition, compound 2 also inhibited a common resistant pathway of pathogens, biofilm formation of S. aureus and MRSA. Moreover, the therapeutic index of 2 is up to 598, which can be viewed as highly selective and having low toxicity to human HEK-293 cells. Although these compounds displayed less effectiveness for the Gram-negative bacterium, Pseudomonas aeruginosa, they still manifested some effects on the virulence properties of P. aeruginosa, such as biofilm formation, pyocyanin production, and swarming motility. In silico analyses of the structure-activity relationship as well as ADMET properties were discussed in the end. This study shed some light on the antibacterial activities of bromophenols.
© 2024 The Authors. Published by American Chemical Society.