Discovery of N,N'-diarylurea molecules with activity against multidrug-resistant Staphylococcus aureus.

Autor: Yeo HH; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan., Jao YH; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan., Yang FW; Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan., Kuo MH; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan., Lee MH; Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan., Shiau CW; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan., Chiu HC; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.; Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan., Su JC; Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Aug; Vol. 357 (8), pp. e2400047. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1002/ardp.202400047
Abstrakt: The emergence and global spread of methicillin-resistant Staphylococcus aureus (MRSA) pose a serious threat to public health, underscoring the urgent need for novel antibacterial interventions. Here, we screened 18 newly synthesized N,N'-diarylurea derivatives to identify compounds with activity against MRSA. Our investigations led to the discovery of a small molecule, SCB-24, which exhibited promising antimicrobial activity against MRSA USA300. Notably, SCB-24 demonstrated high activity even in the presence of 10% fetal bovine serum and showed excellent selectivity for bacterial over mammalian cells. SCB-24 also showed potent activity against various MRSA strains, including those resistant to second- and third-line antibiotics. Importantly, the efficacy of SCB-24 was inferior to that of vancomycin in MRSA-infected Galleria mellonella larvae. Overall, our findings suggest that SCB-24 has great potential as a new therapeutic for multidrug-resistant S. aureus infections.
(© 2024 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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