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.
