Flavonoids, aldose reductase inhibitors

Tetramethyleneglutaric acid (TMG) (62) and alrestatin (AY-22,284) (63)) are known aldose reductase inhibitors. From natural products, a number of flavonoids have been reported to have aldose reductase inhibitory activity. Quercetin (64 1, R = H), quercitrin (64 2, R = L-rhamnose), rutin (64 3, R = rutinose (6-O-a -L-rhamnosyl-D-glucose)) and myricitrin (65 2, R = L-rhamnose) were much more effective inhibitors of aldose reductase from rat lens than TMG (62) and alrestatin (63) [66]. Quercetin with 3, 4 -dihydroxy substitution in ring C was more potent... 

Flavonoids and related phenols, such as catechins and coumarins have been found to be aldose reductase inhibitors. Compounds containing a... 

Lens aldose reductase has been implicated in the pathogenesis of cataracts in diabetic and galac-tosemic animals. The enzyme catalyzes the reduction of glucose and galactose to their polyols, which accumulate in large quantities in the lens and ultimately lead to mature lens opacities. Several key bioflavones have activity against this enzyme. Oral administration of quercitrin decreased the accumulation of sobital in the lens. Therefore, the accumulation of lens opacities could be partially abrogated by certain flavonoids. In a study of 30 flavones, 4 isoflavones, and 13 coumarins, many potent inhibitors were found, but 5,7,3, 4 -tetrahydroxy-3,6-dimethoxyflavone and 6,3, 4 -trihy-droxy-5,7,8-trimethoxyflavone were especially active. 

Amic, D., Davidovic-Amic, D., Beslo, D., Lucic, B. and Trinajstic, N. (1997). The Use of the Ordered Orthogonalized Multivariate Linear Regression in a Structure-Activity Study of Cou-marin and Flavonoid Derivatives as Inhibitors of Aldose Reductase. J.Chem.Inf.Comput.ScL, 37,581-586. 

Varma SD, Mikuni I, Kinoshita JH. Flavonoids as inhibitors of lens aldose reductase. Science 1975 188 1215-1216. 

D. Amid, D. Davidovid-Amid, D. Beslo, B. Lucid, and N. Trinajstid, The use of the ordered orthogonalized mnltivariate linear regression in a structure-activity study of coumarin and flavonoid derivatives as inhibitors of Aldose Reductase, J. Chem. Inf. Comput. Sci. 37 (1997) 581-586. 

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