Structure-activity relationship and crystallographic study of new monobactams

Monobactams, a subclass of β-lactam antibiotics characterized by a monocyclic core, are uniquely resistant to hydrolysis by metallo-β-lactamases, which represents a distinct therapeutic advantage. In this study, we tacked 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, which was used as a model PBP.