Captopril analogues as metallo-β-lactamase inhibitors

Yusralina Yusof; Daniel T C Tan; Omid Khalili Arjomandi; Gerhard Schenk; Ross P McGeary

doi:10.1016/j.bmcl.2016.02.007

Captopril analogues as metallo-β-lactamase inhibitors

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1589-1593. doi: 10.1016/j.bmcl.2016.02.007. Epub 2016 Feb 4.

Authors

Yusralina Yusof¹, Daniel T C Tan¹, Omid Khalili Arjomandi¹, Gerhard Schenk¹, Ross P McGeary²

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia.
² School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia. Electronic address: r.mcgeary@uq.edu.au.

PMID: 26883147
DOI: 10.1016/j.bmcl.2016.02.007

Abstract

A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid.

Keywords: Antibiotic resistance; Captopril; IMP-1 inhibitor; Metallo-β-lactamase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Captopril / analogs & derivatives*
Captopril / chemistry
Captopril / pharmacology*
Dose-Response Relationship, Drug
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
beta-Lactamase Inhibitors / chemical synthesis
beta-Lactamase Inhibitors / chemistry
beta-Lactamase Inhibitors / pharmacology*
beta-Lactamases / metabolism*

Substances

beta-Lactamase Inhibitors
Captopril
beta-lactamase IMP-1
beta-Lactamases