Jump to main content
Jump to site search

Issue 12, 2003
Previous Article Next Article

Design, synthesis and evaluation of bifunctional inhibitors of type II dehydroquinase

Author affiliations

Abstract

Inhibitors of type II dehydroquinase were designed to straddle the two distinct binding sites identified for the inhibitor (1S,3R,4R)-1,3,4-trihydroxy-5-cyclohexene-1-carboxylic acid and a glycerol molecule in a crystallographic study of the Streptomyces coelicolor enzyme. A number of compounds were designed to incorporate characteristics of both ligands. These analogues were synthesized from quinic acid, and were assayed against type I (Salmonella typhi) and type II (S. coelicolor) dehydroquinases. None of the analogues showed inhibition for type I dehydroquinase. Six of the analogues were shown to have inhibition constants in the micromolar to low millimolar range against the S. coelicolor type II dehydroquinase, while two showed no inhibition. The binding modes of the analogues in the active site of the S. coelicolor enzyme were studied by molecular docking with GOLD1.2. These studies suggest a binding mode where the ring is in a similar position to (1S,3R,4R)-1,3,4-trihydroxy-5-cyclohexene-1-carboxylic acid in the crystal structure and the side-chain occupies part of the glycerol binding-pocket.

Graphical abstract: Design, synthesis and evaluation of bifunctional inhibitors of type II dehydroquinase

Back to tab navigation

Supplementary files

Publication details

The article was received on 05 Feb 2003, accepted on 02 May 2003 and first published on 15 May 2003


Article type: Paper
DOI: 10.1039/B301731A
Citation: Org. Biomol. Chem., 2003,1, 2075-2083
  •   Request permissions

    Design, synthesis and evaluation of bifunctional inhibitors of type II dehydroquinase

    M. D. Toscano, M. Frederickson, D. P. Evans, J. R. Coggins, C. Abell and C. González-Bello, Org. Biomol. Chem., 2003, 1, 2075
    DOI: 10.1039/B301731A

Search articles by author

Spotlight

Advertisements