Identification of novel <i>N</i>-benzyloxy-amino acid hydroxamates as inhibitors of the virulence factor LasB from <i>Pseudomonas aeruginosa</i>.

ABSTRACT: The emergence of multidrug-resistant pathogens, particularly Pseudomonas aeruginosa, represents a global health concern. Among its major virulence factors, elastase B (LasB), a zinc-dependent metalloprotease, plays a pivotal role in host tissue degradation, immune evasion, and biofilm formation. Targeting LasB with selective inhibitors offers a promising therapeutic strategy to mitigate bacterial virulence while minimizing selective pressure for resistance development. In this study, a series of N-benzyloxy amino acid derivatives were designed, synthesized, and evaluated for their inhibitory activity against LasB. Structure-based optimization led to the identification of compound 12 as the most potent inhibitor (K _i = 0.92 μM), exhibiting high selectivity fo

SUBMITTER: Di Leo R 

PROVIDER: S-EPMC12352668 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature