Discovery of Pyrrolidine-2,3-diones as Novel Inhibitors of P. aeruginosa PBP3.

ABSTRACT: The alarming threat of the spread of multidrug resistant bacteria currently leaves clinicians with very limited options to combat infections, especially those from Gram-negative bacteria. Hence, innovative strategies to deliver the next generation of antibacterials are urgently needed. Penicillin binding proteins (PBPs) are proven targets inhibited by β-lactam antibiotics. To discover novel, non-β-lactam inhibitors against PBP3 of Pseudomonas aeruginosa, we optimised a fluorescence assay based on a well-known thioester artificial substrate and performed a target screening using a focused protease-targeted library of 2455 compounds, which led to the identification of pyrrolidine-2,3-dione as a potential scaffold to inhibit the PBP3 target. Further chemical optimisation using a one-po

SUBMITTER: Lopez-Perez A 

PROVIDER: S-EPMC8147781 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature