biostudies-literatureUnknown15(3)Canale VMultidrug-resistant (MDR) strains of <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), 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 <b>25</b> was identified, demonstrating potent bacteriostatic activity against clinical multidrug-resistant <i>S. epidermidis</i> strains (MIC₅₀ and MIC₉₀ = 1.6 and 3.125 μg/mL). Importantly, it showed activity against linezolid-resistant strains and exhibited selectivity over mammalian cells. Compound <b>25</b> displayed antibiofilm-forming properties against clinical <i>S. epidermidis</i> strains and demonstrated the capacity to eliminate existing biofilm layers. Additionally, it induced complete depolarization of the bacterial membrane in clinical <i>S. epidermidis</i> strains. In light of these findings, targeting bacterial cell membranes with compound <b>25</b> emerges as a promising strategy in the fight against multidrug-resistant <i>S. epidermidis</i> strains.ACS medicinal chemistry letters369-375https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945555biostudies-literatureImproving Activity of New Arylurea Agents against Multidrug-Resistant and Biofilm-Producing <i>Staphylococcus epidermidis</i>.PMC10945555Zajdel PSkiba-Kurek IKarczewska ERopek MPomierny BCanale VKlesiewicz KPapiez MPiska KEmpel JKoczurkiewicz-Adamczyk PfalseImproving Activity of New Arylurea Agents against Multidrug-Resistant and Biofilm-Producing <i>Staphylococcus epidermidis</i>.Multidrug-resistant (MDR) strains of <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), 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 <b>25</b> was identified, demonstrating potent bacteriostatic activity against clinical multidrug-resistant <i>S. epidermidis</i> strains (MIC₅₀ and MIC₉₀ = 1.6 and 3.125 μg/mL). Importantly, it showed activity against linezolid-resistant strains and exhibited selectivity over mammalian cells. Compound <b>25</b> displayed antibiofilm-forming properties against clinical <i>S. epidermidis</i> strains and demonstrated the capacity to eliminate existing biofilm layers. Additionally, it induced complete depolarization of the bacterial membrane in clinical <i>S. epidermidis</i> strains. In light of these findings, targeting bacterial cell membranes with compound <b>25</b> emerges as a promising strategy in the fight against multidrug-resistant <i>S. epidermidis</i> strains.2024-01-01T00:00:00Z2024 Mar2025-04-26T12:04:59.753Z2025-02-19T03:08:27.335ZS-EPMC109455553850585610.1021/acsmedchemlett.3c00536