Development of covalent inhibitors for bacterial histidine kinases

Abstract

Antivirulence therapies offer an alternative strategy against antimicrobial resistance. We synthesized 2-aminobenzothiazole sulfonyl fluoride analogs for covalent histidine kinase inhibition. In vitro and in cellulo assays also identified lead inhibitors for affinity-based probe development. However, alkyne incorporation reduced bioactivity, emphasizing the challenges of designing functional probes while preserving inhibitor potency.