Inhibition of aldose reductases from rat and bovine lenses by hydantoin derivatives.

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Abstract
The development of potent aldose reductase inhibitors as therapeutic agents for diabetic complications is highly desirable. The inhibitory action of 54 hydantoin derivatives consisting of 25 hydantoins, 21 2-thiohydantoins and 8 2-alkylthiohydantoins was therefore tested on rat and bovine lens aldose reductases in vitro. 1-(Phenylsulfonyl)-hydantoin and its derivatives, 1-[(substituted phenyl)sulfonyl]hydantoins, were potent inhibitors of the enzymes. 1-[(p-Bromophenyl)sulfonyl]hydantoin was the most potent among them. It inhibited purified rat and bovine lens aldose reductases by 50% at 7 .times. 10-7 M and 3.7 .times. 10-7 M, respectively. Inhibition of rat and bovine lens aldose reductases by this compound was due to its non-ionized form, but not the ionized form, and was of a non-competitive type with respect to DL-glyceraldehyde as a substrate.