Screening Of Enzyme Inhibitors And Their Bioactivity

The enzyme inhibitor is a type of compound that specifically blocks the action of an enzyme and reduces its activity, mainly derived from plants, microorganisms and chemical synthesis, the development of enzyme inhibitors is a major pathway for drug discovery. Currently, there are many classes of enzyme inhibitors in the market and more and more disease targeting enzyme inhibitors are continuing to enter the market. a-Glucosidase inhibitors act as competitive inhibitors of intestinal a-Glucosidase, reduce the rate of digestion of carbohydrates, delay the absorption of glucose and decrease postprandial blood glucose levels.1-Deoxynojirimycin (DNJ) is a polyhydroxylated piperidine alkaloid with a similar structure to glucose, serving as an effective inhibitor of a-glucosidase. Thirteen1-deoxynojirimycin (DNJ) derivatives of five different skeletal structures were evaluated using an in vitro a-glucosidase assay, and kinetic parameters (Ki, IC50) were measured. Some DNJ derivatives showed weak a-glucosidase inhibitory activities, and the compounds1-(3-benzyloxy-2-hydroxy propyl)-2-hydroxymethyl-piperidine-3,4,5-triol(la), and1-{3-[1-(4-fluorophenyl)-1H-[1,2,3]triazol-4-ylmethoxy]-2-hydroxypropyl}-2-hydrox ymethyl-piperidine-3,4,5-triol (8d) showed activities comparable to that of DNJ, exhibiting great potential in diabetes treatment. Indoleamine2,3-dioxygenase (IDO), the first and rate-limiting enzyme in the kynurenine pathway (KP) of tryptophan catabolism, is recently established as one of the key players involved in the pathogenesis of Alzheimer’s disease (AD). IDO inhibition has attracted significantly increasing attention in pharmaceutical, clinical and therapeutic studies for AD treatment. Here, we characterized the effects of AH-1in a mouse model of AD on the basis of its IDO inhibitory ability. Our results showed that AH-1was an efficient uncompetitive IDO inhibitor, more potent than1-methyl-tryptophan (1-MT), the most frequently used competitive inhibitor of IDO. In a mouse model of AD,, oral administration of AH-1for one month significantly ameliorated impaired cognition, reduced amyloid plaque formation, prevented neuron loss and decreased the activation of microglia and astrocytes. These findings give further evidence to support the critical links between IDO, KP and AD, and demonstrate the potential for a new class of drugs for AD treatment.