title: Flavonoids: true or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase.
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.
authors: Université de Strasbourg/CNRS, Strasbourg, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France. Electronic address: dtritsch@unistra.fr.
authors: Denis
authors: D
authors: Tritsch
authors: Université de Strasbourg/CNRS, Strasbourg, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France.
authors: Catherine
authors: C
authors: Zinglé
authors: Université de Strasbourg/CNRS, Strasbourg, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France.
authors: Michel
authors: M
authors: Rohmer
authors: Université de Strasbourg/CNRS, Strasbourg, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France. Electronic address: grosdemange@unistra.fr.
authors: Catherine
authors: C
authors: Grosdemange-Billiard
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D004927:Escherichia coli Infections / Q000382:microbiology; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases
keywords: 1-Deoxyxylulose 5-phosphate reductoisomerase; 2-C-methyl-D-erythritol 4-phosphate pathway; Flavonoids; Promiscuous inhibition