Flavonoids: true or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase

Bioorg Chem. 2015 Apr;59:140-4. doi: 10.1016/j.bioorg.2015.02.008. Epub 2015 Feb 28.

Abstract

Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC50 values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings.

Keywords: 1-Deoxyxylulose 5-phosphate reductoisomerase; 2-C-methyl-D-erythritol 4-phosphate pathway; Flavonoids; Promiscuous inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldose-Ketose Isomerases / antagonists & inhibitors*
  • Aldose-Ketose Isomerases / metabolism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli Infections / microbiology
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology*
  • Humans

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • 1-deoxy-D-xylulose 5-phosphate reductoisomerase
  • Aldose-Ketose Isomerases