2-Sulfonylpyrimidines as Privileged Warheads for the Development of S. aureus Sortase A Inhibitors.

ABSTRACT: Staphylococcus aureus is one of the most frequent causes of nosocomial and community-acquired infections, with emerging multiresistant isolates causing a significant burden to public health systems. We identified 2-sulfonylpyrimidines as a new class of potent inhibitors against S. aureus sortase A acting by covalent modification of the active site cysteine 184. Series of derivatives were synthesized to derive structure-activity relationship (SAR) with the most potent compounds displaying low micromolar K_I values. Studies on the inhibition selectivity of homologous cysteine proteases showed that 2-sulfonylpyrimidines reacted efficiently with protonated cysteine residues as found in sortase A, though surprisingly, no reaction occurred with the more nucleophilic cyste

SUBMITTER: Barthels F 

PROVIDER: S-EPMC8763382 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature