N-acylated sulfonamide congeners of fosmidomycin lack any inhibitory activity against DXR

Bioorg Med Chem Lett. 2015 Apr 1;25(7):1577-9. doi: 10.1016/j.bmcl.2015.02.006. Epub 2015 Feb 12.

Abstract

The antibiotic fosmidomycin (3a) is an inhibitor of the non-mevalonate pathway for isoprenoid biosynthesis. Four analogues in which an acylated sulfonamide group is substituting for its phosphonate moiety have been synthesized in a fruitless effort to preserve one negative charge in order to increase the accompanying affinity for 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the fosmidomycin target enzyme.

Keywords: Antimalarial; DXR inhibitors; Fosmidomycin; N-Acyl sulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Aldose-Ketose Isomerases / metabolism*
  • Anti-Bacterial Agents / chemistry*
  • Escherichia coli / enzymology
  • Fosfomycin / analogs & derivatives*
  • Fosfomycin / chemistry
  • Molecular Structure
  • Sulfonamides / chemistry*

Substances

  • Anti-Bacterial Agents
  • Sulfonamides
  • Fosfomycin
  • fosmidomycin
  • 1-deoxy-D-xylulose 5-phosphate reductoisomerase
  • Aldose-Ketose Isomerases