Comprehensive Exploration\nof Bromophenol Derivatives:\nPromising Antibacterial Agents against SA and MRSA

The incidence of treatment failure due to multidrug-resistant\npathogens\nelevated over the years; the rate is much higher than new antibiotic\ndrug discovery. Therefore, bromophenol derivatives as potential antibacterial\nagents on Staphylococcus aureus and\nMRSA were explored in this research via integrating chemistry, microbiology,\nand pharmacology to address significant knowledge gaps pertaining\nto the antibacterial activity of bromophenols based on their functional\ngroups. Surprisingly, a simple molecule, 3-bromo-2,6-dihydroxyacetophenone\n(<b>2</b>), exhibited good anti-S. aureus activity and even MRSA, a drug-resistant strain. In addition, compound <b>2</b> also inhibited a common resistant pathway of pathogens,\nbiofilm formation of S. aureus and\nMRSA. Moreover, the therapeutic index of <b>2</b> is up to 598,\nwhich can be viewed as highly selective and having low toxicity to\nhuman HEK-293 cells. Although these compounds displayed less effectiveness\nfor the Gram-negative bacterium, Pseudomonas aeruginosa, they still manifested some effects on the virulence properties\nof P. aeruginosa, such as biofilm formation,\npyocyanin production, and swarming motility. <i>In silico</i> analyses of the structure–activity relationship as well as\nADMET properties were discussed in the end. This study shed some light\non the antibacterial activities of bromophenols.