Potential Inhibitors Against NDM-1 Type Metallo-β-Lactamases: An Overview

Microb Drug Resist. 2020 Dec;26(12):1568-1588. doi: 10.1089/mdr.2019.0315. Epub 2020 Jun 2.

Abstract

A new member of the class metallo-β-lactamase (MBL), New Delhi metallo-beta-lactamase 1 (NDM-1) has emerged recently as a leading threat to the treatment of infections that have spread in all major Gram-negative pathogens. The enzyme inactivates antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. This review provides information about NDM-1 spatial structure, potential features of the active site, and its mechanism of action. It also enlists the inhibitors/compounds/drugs against NDM-1 in various development phases. Understanding their mode of inhibition and the structure-activity relationship would be beneficial for development, synthesis, and even increasing biological efficacy of inhibitors, making them more promising drug candidates.

Keywords: MBL; NDM-1 inhibitors; beta lactamase; developmental phase; multi drug resistant; peptidoglycan.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Penicillin-Binding Proteins / drug effects
  • Structure-Activity Relationship
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / chemistry*
  • beta-Lactamases / drug effects
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Penicillin-Binding Proteins
  • beta-Lactamase Inhibitors
  • beta-Lactamases
  • beta-lactamase NDM-1