Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as β-lactamase substrates

Ahmad Ghavami, Geneviève Labbé, Jürgen Brem, Valerie J Goodfellow, Laura Marrone, Carol A Tanner, Dustin T King, Melinda Lam, Natalie C J Strynadka, Dylan R Pillai, Stefan Siemann, James Spencer, Christopher J Schofield, Gary I Dmitrienko

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)

Abstract

We report on the synthesis of three nitrocefin analogues and their evaluation as substrates for the detection of β-lactamase activity. These compounds are hydrolyzed by all four Ambler classes of β-lactamases. Kinetic parameters were determined with eight different β-lactamases, including VIM-2, NDM-1, KPC-2, and SPM-1. The compounds do not inhibit the growth of clinically important antibiotic-resistant gram-negative bacteria in vitro. These chromogenic compounds have a distinct absorbance spectrum and turn purple when hydrolyzed by β-lactamases. One of these compounds, UW154, is easier to synthesize from commercial starting materials than nitrocefin and should be significantly less expensive to produce.

Original languageEnglish
Pages (from-to)75-7
Number of pages3
JournalAnalytical Biochemistry
Volume486
DOIs
Publication statusPublished - 1 Oct 2015

Keywords

  • Biocatalysis
  • Cephalosporins
  • Chemistry Techniques, Synthetic
  • Drug Evaluation, Preclinical
  • Hydrolysis
  • Kinetics
  • beta-Lactamases

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