ArticleBioorganic & medicinal chemistry letters2025
Phenyl urea based adjuvants for β-lactam antibiotics against methicillin resistant Staphylococcus aureus.
Article in Bioorganic & medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Exploration of a benzothiophene scaffold for use as adjuvants with β-lactam antibiotics against methicillin-resistantRSC medicinal chemistry · 2026Article
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Authors and funding
10 authors.
Funding
Abstract
Penicillin binding protein 4 (PBP4) is essential for Staphylococcus aureus cortical bone osteocyte lacuno-canalicular network (OLCN) invasion, which causes osteomyelitis and serves as a bacterial niche for recurring bone infection. Moreover, PBP4 is also a key determinant of S. aureus resistance to fifth-generation cephalosporins (ceftobiprole and ceftaroline). From these perspectives, the development of S. aureus PBP4 inhibitors may represent dual functional therapeutics that prevent osteomyelitis, and reverse PBP4-mediated β-lactam resistance. A high-throughput screen for small molecules that inhibit S. aureus PBP4 function identified compound 1. We recently described a preliminary structure activity relationship (SAR) study on 1, identifying several compounds with increased PBP4 inhibitory activity, some of which also inhibit PBP2a. Herein, we expand our exploration of phenyl ureas as antibiotic adjuvants, investigating their activity with penicillins and additional cephalosporins against PBP2a-mediated methicillin-resistant S. aureus (MRSA). We screened the previously reported pilot library, and prepared an additional series of phenyl ureas based on compound 1. Lead compounds potentiate multiple β-lactam antibiotics, lowering minimum inhibitory concentrations (MICs) below susceptibility breakpoints, with up to 64-fold reductions in MIC.
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