Elucidation of critical chemical moieties of metallo-β-lactamase inhibitors and prioritisation of target metallo-β-lactamases

J Enzyme Inhib Med Chem. 2024 Dec;39(1):2318830. doi: 10.1080/14756366.2024.2318830. Epub 2024 Mar 15.

Abstract

The urgent demand for effective countermeasures against metallo-β-lactamases (MBLs) necessitates development of novel metallo-β-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Keywords: Metallo-β-lactamase inhibitor; chemical moiety; metallo-β-lactamase variant type.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Drug Design
  • beta-Lactamase Inhibitors* / pharmacology
  • beta-Lactamases*

Substances

  • beta-Lactamase Inhibitors
  • beta-Lactamases
  • Anti-Bacterial Agents

Grants and funding

This work was supported by research grants from the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communications Technology (MSIT; grant No. NRF-2017M3A9E4078014); and from the NRF funded by the MSIT (grant Nos. NRF-2021R1A2C3004826 and NRF-2022R1F1A1074068).