Improving Activity of New Arylurea Agents against Multidrug-Resistant and Biofilm-Producing .

Multidrug-resistant (MDR) strains of (), prevalent in hospital environments, contribute to increased morbidity and mortality, especially among newborns, posing a critical concern for neonatal sepsis. In response to the pressing demand for novel antibacterial therapies, we present findings from synthetic chemistry and structure-activity relationship studies focused on arylsulfonamide/arylurea derivatives of aryloxy[1-(thien-2-yl)propyl]piperidines. Through bioisosteric replacement of the sulfonamide fragment with a urea moiety, compound was identified, demonstrating potent bacteriostatic activity against clinical multidrug-resistant strains (MIC and MIC = 1.6 and 3.125 μg/mL). Importantly, it showed activity against linezolid-resistant strains and exhibited selectivity over mammalian cells. Compound displayed antibiofilm-forming properties against clinical strains and demonstrated the capacity to eliminate existing biofilm layers. Additionally, it induced complete depolarization of the bacterial membrane in clinical strains. In light of these findings, targeting bacterial cell membranes with compound emerges as a promising strategy in the fight against multidrug-resistant strains.