Discovery of N,N'-diarylurea molecules with activity against multidrug-resistant Staphylococcus aureus.
Journal
Archiv der Pharmazie
Journal Volume
357
Journal Issue
8
ISSN
1521-4184
Date Issued
2024-08
Author(s)
Yeo, Hui-Hui
Jao, Yu-Hsuan
Yang, Fan-Wei
Kuo, Min-Hsuan
Lee, Meng-Hsuan
Shiau, Chung-Wei
Su, Jung-Chen
DOI
10.1002/ardp.202400047
Abstract
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.
Subjects
MRSA
N,N’‐diarylurea
PK150
Staphylococcus aureus
SDGs
Description
Article number 2400047
Type
journal article