A Cephalosporin-Tripodalamine Conjugate Inhibits Metallo-β-Lactamase with High Efficacy and Low Toxicity.

ABSTRACT: The wide spread of metallo-β-lactamase (MBL)-expressing bacteria has greatly threatened human health, and there is an urgent need for inhibitors against MBLs. Herein, we present a cephalosporin-tripodalamine conjugate (DPASC) as a potent MBL inhibitor with a block-release design. The cephalosporin tag blocks the ligand binding site to reduce toxicity and is cleaved by MBLs to release active ligands to inhibit MBLs in situ. The screening of MBL-expressing pathogenic strains with 16 μg/mL DPASC showed a decrease of the minimum inhibitory concentration of meropenem (MEM) by 16 to 512-fold, and its toxicity was minimal to human HepG2 cells, with an IC₅₀ exceeding 512 μg/mL. An in vivo infection model with Galleria mellonella larvae showed an increased 3-day survival ra

SUBMITTER: Tian H 

PROVIDER: S-EPMC9578398 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature