Identification of simple arylfluorosulfates as potent agents against resistant bacteria

Sulfur fluoride exchange (SuFEx), a next generation of click chemistry, opens an avenue for drug discovery. We report here the discovery and structure-activity relationship studies of a series of arylfluorosulfates, synthesized via SuFEx, as antibacterial agents. Arylfluorosulfates 3, 81, and 101 showed potency to overcome multidrug resistance and were not susceptible to the generation of resistance. They exhibited rapid bactericidal potency and selectively killed gram-positive bacterial strains. These compounds also exhibited the ability to disrupt established bacterial biofilm and kill persisters derived from biofilm. Furthermore, arylfluorosulfate 3 had a synergistic effect with streptomycin and gentamicin. In addition, their anti-MRSA potency was evaluated and determined by the Caenorhabditis elegans model.

Automated summary

A series of arylfluorosulfates synthesized via SuFEx, including compounds 3, 81, and 101, showed potent antibacterial activity, the ability to overcome multidrug resistance, and a lack of susceptibility to resistance development. These compounds also demonstrated rapid bactericidal potency, selectivity against gram-positive bacteria, and the capability to disrupt bacterial biofilms and kill persisters. Additionally, compound 3 exhibited synergy with streptomycin and gentamicin, while their anti-MRSA activity was evaluated using the Caenorhabditis elegans model.