Yeo, Hui-HuiHui-HuiYeoJao, Yu-HsuanYu-HsuanJaoYang, Fan-WeiFan-WeiYangKuo, Min-HsuanMin-HsuanKuoLee, Meng-HsuanMeng-HsuanLeeShiau, Chung-WeiChung-WeiShiauHAO-CHIEH CHIUSu, Jung-ChenJung-ChenSu2024-12-162024-12-162024-0803656233https://scholars.lib.ntu.edu.tw/handle/123456789/723860Article number 2400047The 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.enfalseMRSAN,N’‐diarylureaPK150Staphylococcus aureus[SDGs]SDG3journal article10.1002/ardp.202400047386879102-s2.0-85191783083