Hydantoin derivative dimers as broad-spectrum antimicrobial agents against ESKAPE pathogens with enhanced killing rate and stability.

A new series of hydantoin derivative dimers as potential broad-spectrum antibiotic agents is designed and synthesized to combat ESKAPE pathogens. As membrane-active antimicrobial agents, in addition to cationic charged and hydrophobic groups that mimic AMPs (antimicrobial peptides), hydantoin backbones and aromatic linkers increased the rigidity and lipophilicity of the designed compounds, thus improving the stability and bactericidal killing rate. After whole cell phenotypic screening against eight bacterial strains, including MRSA (methicillin-resistant ), compound 18 was chosen as the lead compound with overall excellent broad-spectrum antibacterial activity (GM = 7.