20.500.12556/RUL-163495 Synthesis and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s) In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from Streptococcus pneumoniae. Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity. antibacterial agents monocyclic-β-lactams penicillin-binding proteins covalent inhibitors transpeptidase antibakterijska sredstva monociklični β-laktami proteini ki vežejo penicilin kovalentni inhibitorji transpeptidaza farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2024-10-08 08:50:38 2024-10-08 08:50:44 2024-10-10 03:38:53 0000-00-00 00:00:00 2024 0 0 Str. 423-440 no. 3 Vol. 74 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54 1846-9558 10.2478/acph-2024-0024 206045187 Synthesis-and-biochemical-evaluation-of-new-3amido4substituted-monocyclic-lactams-as-inhibitors-of-penicillinbinding-proteins.pdf Synthesis-and-biochemical-evaluation-of-new-3amido4substituted-monocyclic-lactams-as-inhibitors-of-penicillinbinding-proteins.pdf 1 25B7CABCAFB9E4B9298ADF40B68FAF61 c876282ec9b6044d75894b3f7114530a928d7ce3aa201749ad9b69f383b909cf da6c488b-8545-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=193247 https://acta.pharmaceutica.farmaceut.org/wp-content/uploads/2024/09/42324.pdf 1 776c09e0-8541-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=193232 Fakulteta za farmacijo Veterinarska fakulteta 0 0 0