1-Benzopyran-4-one antioxidants as aldose reductase inhibitors

Starting from the inhibitory activity of the flavonoid Quercetin, a series of 4H-1-benzopyran-4-one derivatives was synthesized and tested for inhibit ion of aldose reductase, an enzyme involved in the appearance of diabetic c omplications. Some of the compounds obtained display inhibitory activity si milar to that of Sorbinil but are more selective than Quercetin and Sorbini l with respect to the closely related enzyme, aldehyde reductase, and also possess antioxidant activity. Remarkably, these compounds possess higher pK (a) values than carboxylic acids, a characteristic which could make the pha rmacokinetics of these compounds very interesting. Molecular modeling inves tigations on the structures of inhibitors bound at the active site of aldos e reductase were performed in order to suggest how these new inhibitors mig ht bind to the enzyme and also to interpret structure-activity relationship s.