%0 Journal Article
%T Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as β-lactamase substrates.
%A Ghavami A
%A Labbé G
%A Brem J
%A Goodfellow VJ
%A Marrone L
%A Tanner CA
%A King DT
%A Lam M
%A Strynadka NC
%A Pillai DR
%A Siemann S
%A Spencer J
%A Schofield CJ
%A Dmitrienko GI
%J Anal Biochem
%V 486
%N 0
%D Oct 2015 1
%M 26142222
%F 3.191
%R 10.1016/j.ab.2015.06.032
%X 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.