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

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 (18) and its derivatives, 1-[(substituted phenyl) sulfonyl] hydantoins, were found to be potent inhibitors of the enzymes. 1-[(p-Bromophenyl) sulfonyl] hydantoin (49) was the most potent among them. It inhibited purified rat and bovine lens aldose reductases by 50% at 7×10-7M and 3.7×10-7M, respectively. Inhibition of rat and bovine lens aldose reductases by this compound (49) 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.