Discovery and development of substituted thiadiazoles as inhibitors of Staphylococcus aureus Sortase A.

Basic Information

ID: ALA4396929

Journal: Bioorg Med Chem

Title: Discovery and development of substituted thiadiazoles as inhibitors of Staphylococcus aureus Sortase A.

Authors: Wehrli PM, Uzelac I, Olsson T, Jacso T, Tietze D, Gottfries J.

Abstract: High-throughput screening of small-molecule libraries has led to the identification of thiadiazoles as a new class of inhibitors against Staphylococcus aureus sortase A (SrtA). N-(5-((4-nitrobenzyl)thio)-1,3,4-thiadiazol-2-yl)nicotinamide (IC₅₀ = 3.8 µM) was identified as a potent inhibitor of SrtA after synthetic modification of hit compounds. Additional ligands developed in this study displayed affinities in the low micromolar range without affecting bacterial growth in vitro. The study also suggest a new mode of action through covalent binding to the active site cysteine.

CiteXplore: 31420255

DOI: 10.1016/j.bmc.2019.115043

Patent ID: ┄