New Potent Sulfonamide-Based Inhibitors of <i>S</i>. <i>aureus</i> Biotin Protein Ligase.

ABSTRACT: The key regulatory metabolic enzyme, biotin protein ligase (BPL), is an attractive target for the development of novel antibiotics against multi-drug-resistant bacteria, such as Staphylococcus aureus. Here we report the synthesis and assay of a new series of inhibitors (6-9) against S. aureus BPL (SaBPL), where a component sulfonamide linker was used to mimic the acyl-phosphate group of the natural intermediate biotinyl-5'-AMP (1). A pivotal correlation between the acidity of the central NH of the sulfonamide linker of 6-9 and in vitro inhibitory activity against SaBPL was observed. Specifically, sulfonylcarbamate 8, with its highly acidic sulfonyl central NH, as evaluated by ¹H NMR spectroscopy,

SUBMITTER: Stachura DL 

PROVIDER: S-EPMC11403734 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature