[Aldose reductase inhibitors].

Abstract

Aldose reductase (AR) is an enzyme which catalyzes the transformation of D-glucose to sorbitol. Under non physiological conditions, like diabetes for example, the accumulation of polyols in the lens, sorbitol in particular, gives a basis to the osmotic hypothesis of cataract formation. AR inhibitors can protect against such accumulation. Oxidation of the constituents of the lens is a primary phenomenon in cataract formation, and some authors have suggested that the autoxidation of monosaccharides would originate the formation of cataract. For these authors, AR inhibitors would act by trapping the radical intermediates formed, inhibiting the denaturation of proteins in the organ and the lowering of glutathione. There classes of AR inhibitors can be distinguished: flavonoids and their related compounds, spirohydantoins--like sorbinil--and related compounds, and compounds with an acid function such as alrestatine. For each of these three classes, the authors try to establish the structure-activity relationship of the molecules. The possibility of a single site of interaction between AR and the different AR inhibitors is discussed. Differences in the inhibitory effect for a given compound between species, and for one species between tissues have been underlined.