Sustainable Joullie-Ugi and Continuous Flow Implementation Led to Novel Captopril-Inspired Broad-Spectrum Metallo-β-Lactamase Inhibitors.

ABSTRACT: Metallo-β-lactamases (MBL) production is one of the most alarming bacterial resistance mechanisms, conferring broad-spectrum resistance to most β-lactam antibiotics and combinations with β-lactamase inhibitors. Since no MBL inhibitors have been approved yet, the quest for novel, safe, and effective compounds, possibly endowed with broad-spectrum activity against clinically relevant MBLs, represents an urgent clinical need. Inspired by captopril, which behaves as a weak MBL inhibitor, we herein report a continuous flow protocol for the generation of new MBL inhibitors. We employed a Joullié-Ugi multicomponent reaction for generating two indoline-based subseries, reproducing the captopril binding mode, while increasing the hydrophobic interactions within the MBL active site. Interaction betw

SUBMITTER: Alfano AI 

PROVIDER: S-EPMC12406192 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature