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

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.