These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Stereochemically altered cephalosporins as potent inhibitors of New Delhi metallo-β-lactamases.
    Author: Hu L, Yang H, Yu T, Chen F, Liu R, Xue S, Zhang S, Mao W, Ji C, Wang H, Xie H.
    Journal: Eur J Med Chem; 2022 Mar 15; 232():114174. PubMed ID: 35152091.
    Abstract:
    Antibiotic resistance caused by β-lactamases, particularly metallo-β-lactamases, has been a major threat to public health globally. New Delhi metallo-β-lactamase-1 (NDM-1) represents one of the most important metallo-β-lactamases; the production of NDM-1 in bacterial pathogen significantly reduces the efficacy of β-lactam antibiotics, including life-saving carbapenems. Herein, we have demonstrated stereochemically altered cephalosporins as potent inhibitors against NDM-1, as well as mutants of NDM. The structure and activity relationship (SAR) study on over twenty cephalosporin analogues discloses the stereochemistry and the substituents on 7-position and 3'-position of cephalosporin are critical to suppress the activity of NDM-1 and the optimal compound 1u exhibited an IC50 of 0.13 μM. Furthermore, a crystal complex of NDM-1 and 1u has been obtained, suggesting this cephalosporin derivative inhibits enzyme activity by the formation of a relatively stable hydrolytic product-NDM-1 intermediate. The discovery in this study may pave the way to turn cephalosporin, a natural substrate of β-lactamase, into an effective NDM-1 inhibitor to combat antibiotic resistance.
    [Abstract] [Full Text] [Related] [New Search]