Synthesis and biological evaluation of irreversible inhibitors of aldose reductase.
5-Isothiocyanatoalrestatin (1b) and 5-azidoalrestatin (1c) were prepared synthetically and examined as potential affinity and photoaffinity inhibitors of rat lens aldose reductase. Both compound 1b and 1c under appropriate conditions at 10(-4) M produced a 70% irreversible inactivation of aldose reductase within 1 min. The enzyme could, in part, be protected by preincubation with sorbinil 2, a known potent inhibitor of aldose reductase.
D000345:Affinity Labels; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D000345:Affinity Labels; D007093:Imidazoles; D048289:Imidazolidines; D007546:Isoquinolines; C050651:5-azidoalrestatin; C050652:5-isothiocyanatoalrestatin; C016212:alrestatin; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil