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Volume 21, Issue 16
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Prevalence of microbial resistance due to Metallo-β-lactamase (MBL) enzyme pose a serious threat to human life. MBLs depend on active site zinc for their hydrolytic activity; hence, the investigation of zinc chelators emerged as an attractive strategy for the development of potent MBL inhibitors.

Methods

To prove that such chelators selectively target MBLs, in the present investigation, novel cephalosporins based MBL inhibitors (Cef-MBLi) were designed as a conjugate of cephalosporins with a potent zinc binder 8-thioquinoline (8-TQ).

Results

Cef-MBLi showed site specific release of conjugate only in the presence of a Verona-integron encoded metallo-β-lactamase 2 (VIM-2) bacterial enzyme through hydrolytic cleavage mechanism. A total of 6 ( and ) New Chemical Entities (NCE’s) were prepared, characterized and subjected for study.

Conclusion

Among tested NCE’s, showed potent MBL inhibitory activity against the VIM-2 enzyme.

© 2024 Bentham Science Publishers
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2024-04-24
2024-12-23

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Design and Biological Evaluation of Cephalosporin based Metallo-β-lactamase (MBL) Inhibitors#
Letters in Drug Design & Discovery 21, 3506 (2024); https://doi.org/10.2174/0115701808287192240415062148
/content/journals/lddd/10.2174/0115701808287192240415062148
/content/journals/lddd/10.2174/0115701808287192240415062148
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Supplements

The supporting information (SI) available as a separate document, which contains further information about IR, NMR MS and HPLC spectral data of synthesized compounds. Supplementary material is available on the publisher's website along with the published article.

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  • Article Type:     Research Article
Keyword(s): 8-thioquinoline (8-TQ); Antibiotic (Abs); antibiotic resistance; cephalosporin based MBL inhibitors (Cef-MBLi); conjugates; enzyme inhibition; metallo-β-lactamase (MBL) enzymes

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