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

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

Bioorganic & Medicinal Chemistry 27 (19) 115043 [2019-10-00; online 2019-10-00]

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 (IC 50 = 3.8 ┬ÁM) 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.

Chemical Biology Consortium Sweden (CBCS) [Service]

Glycoproteomics and MS Proteomics [Service]

Swedish NMR Centre (SNC) [Service]

PubMed 31420255

DOI 10.1016/j.bmc.2019.115043

Crossref 10.1016/j.bmc.2019.115043

Publications 9.5.0