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

• Possible erroneous conclusions regarding the inhibition of enzymes by flavonoids.
• Hydrophobic molecules can generate aggregates responsible of enzyme inhibition.
• Inhibition studies with flavonoids require additional testing with non-ionic detergent.
• Flavonoids inhibit deoxyxylulose phosphate reductoisomerase via a non-specific way.

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.

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