Discovery of sulfone containing metallo-β-lactamase inhibitors with reduced bacterial cell efflux and histamine release issues.

The design, syntheses and antibacterial evaluation of sulfone analogues of previously disclosed metallo-β-lactamase inhibitors (MBLis) are described. The novel derivatives were overall more effective in gram-negative bacterial cell-based assays when combined with imipenem and relebactam. The major contributors to the improved anti-bacterial activity are enhanced enzyme-inhibitor interactions and reduced bacterial cell efflux monitored via an efflux assay involving isogenic Pseudomonas aeruginosa efflux + and efflux - tool strains.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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