20.500.12556/RUL-180892 Structure–activity relationship and crystallographic study of new monobactams Monobactams, a subclass of β-lactam antibiotics with a monocyclic scaffold, are uniquely resistant to hydrolysis by metallo-β-lactamases, providing a distinct therapeutic advantage. Here, we report an in silico-based structure–activity relationship (SAR) investigation of aztreonam-related monobactams. A focused library of monobactam derivatives was synthesized and evaluated for inhibition of penicillin-binding proteins (PBPs) and antibacterial activity. Ten compounds, including aztreonam, were crystallized with truncated PBP1b from Streptococcus pneumoniae, used as a model PBP. Potent PBP1b inhibitors were developed, although high enzymatic potency was not always reflected in strong antibacterial activity. Certain derivatives showed activity against Staphylococcus aureus, which is typically resistant to monobactams. 2D similarity search identified potent inhibitors active against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Crystal structures revealed previously unrecognized binding interactions, including a halogen bond with a conserved threonine residue, underscoring the potential of these interactions to support the development of more potent PBP inhibitors. antimicrobial agents bacteria inhibition inhibitors potassium protimikrobna sredstva bakterije inhibitorji zaviralci derivati ​​monobaktama farmacevtska kemija kalij true false true Angleški jezik Slovenski jezik Članek v reviji 2026-03-19 07:44:19 2026-03-19 07:44:23 2026-09-25 04:27:50 0000-00-00 00:00:00 2026 0 0 Str. 3887-3901 iss. 4 Vol. 69 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54 1520-4804 10.1021/acs.jmedchem.5c02427 271169027 structure-activity-relationship-and-crystallographic-study-of-new-monobactams.pdf structure-activity-relationship-and-crystallographic-study-of-new-monobactams.pdf 1 9BE597E6707771D11C3EC99A7F79FAC9 be1d4a8b9388fa2fee7d95bdd27a02b5731c0e10cf423c088267191ff1118433 09a3e253-b7e7-11f1-8bc5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=248857 https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.5c02427 1 fcb61ca7-235e-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=230837 Fakulteta za farmacijo Veterinarska fakulteta 0 0 0