Article Figures & Data
Figures
- FIG. 1.
Structural representation of sulfonyl hydrazone derivatives (a) and cephalosporins (b). Bonds and atoms in bold depict structural similarities between the classes of compounds.
- FIG. 2.
Structural representation of compounds 14 and 15 and their IC50s.
- FIG. 3.
Dixon (A) and Cornish-Bowden (B) plots illustrating mixed-type inhibition of IMP-1-mediated nitrocefin hydrolysis by compound 6a. The inhibitor constant (Ki) was estimated by graphic analysis of the Dixon plot. Since Dixon plots are not suited for distinguishing between competitive and mixed-type inhibition kinetics, Cornish-Bowden plots were used to determine the mode of inhibition. V, initial rate (velocity) of the reaction; S, substrate concentration.
- FIG. 4.
Stereoviews depicting the active sites of the modeled complexes of sulfonyl hydrazones 1 (A) and 2c (B) with the IMP-1 metallo-β-lactamase. The models are based on the published coordinates of an enzyme-mercaptocarboxylate inhibitor complex (7). Inhibitors and selected amino acid residues lining the binding site and discussed in the text are shown in capped-stick representation (carbon, gray; nitrogen, blue; oxygen, red; sulfur, yellow). The numbers shown denote the positions of amino acid residues in the primary structure of the enzyme. The zinc ions are depicted as large magenta spheres. Water molecules, which are proposed to contribute to a network of favorable interactions between the inhibitor and the protein (see the text), are shown as small red spheres.
Tables
- TABLE 1.
Influence of sulfonyl hydrazones on IMP-1-mediated nitrocefin hydrolysisa
- TABLE 2.
Effect of replacement of a 2-hydroxynaphthyl group on the inhibitory activity of sulfonyl hydrazones against IMP-1
- TABLE 3.
Inhibitory activity of various 2-hydroxynaphthyl, 2 methoxynaphthyl, and anthracyl derivatives on IMP-1-mediated nitrocefin hydrolysis
