Glucosidase inhibitor

The intestinal oligo- and disaccharidases are fixed components of the cell membrane of the brush border region of the wall of the small intestine. These enzymes digest dietary carbohydrate to monosaccharides which are absorbed through the intestinal wall. They include sucrase, maltase, isomaltase, lactase, trehalase, and hetero-p-glucosidase. In the late 1970s, it was realized that inhibition of all or some of these activities could regulate the absorption of carbohydrate, and that these inhibitors could 

---

Acarbose is a nonabsorbable a-glucosidase inhibitor which blocks the digestion of starch, sucrose, and maltose. The digestion of complex carbohydrates is delayed and occurs throughout the small intestine rather than in the upper part of the jejunum. Absorption of glucose and other monosaccharides is not affected. Acarbose is adrninistered orally three times a day and chewed with the first mouthful of food. 

Deoxy-2-fluoroglucosides ( ) are mechanism-based glucosidase inhibitors Fluorine at C-2 slows the rate of the acetal C-OR (R = 2,4-dinitrophenyl) bond cleavage in S by destabilizing the proposed oxocarbonium lon-like transition state for glucosidase-catalyzed hydrolyses [28]... 

The first member of this class, acarbose, was introduced in the early 1990s. a-Glucosidase inhibitors slow the intestinal process of carbohydrate digestion by competitive inhibition of the activity of a-glucosidase enzymes located in the brush border of the enterocytes... 

When a-glucosidase activity is inhibited, carbohydrate digestion is prolonged and takes place further along the intestinal tract. This in turn delays and spreads the period of glucose absorption, which reduces the extent of the postprandial rise in blood glucose concentrations. The effectiveness of a-glucosidase inhibitors is dq en-dent on the consumption of a meal rich in complex carbohydrate. 

The a-glucosidase inhibitors, acarbose (Precose) and miglitol (Glyset), lower blood sugar by delaying die digestion of carbohydrates and absorption of carbohydrates in the intestine. 

The a-glucosidase inhibitors are contraindicated in patients with a hypersensitivity to the drug, diabetic ketoacidosis, cirrhosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to intestinal obstruction, or chronic intestinal diseases. Acarbose and miglitol are used cautiously in patients with renal impairment or pre-existing gastrointestinal (GI) problems such as irritable... 

In order to develop potent D-glucosidase inhibitors, a synthesis of carba-disaccharides containing valiolamine (205) was attempted by Horii and his coworkers utilizing method c. Coupling 205 with the 4-ketose 403, using NaBHjCN and hydrochloric acid, was effective in DMF, giving, after deprotection, the epimeric carba-disaccharides (404 and 405). The saturated... 

The convenient approach to analogs of the naturally occurring glucosidase inhibitor salacinol, was presented by Pinto.58 In a number of papers he described the synthesis of such derivatives. The general motif is shown in Fig. 42. 

Acarbose is an intestinal a-glucosidase inhibitor that delays digestion and absorption of starch and sucrose. It is used in diabetes mellitus and is contraindicated in inflammatory bowel disease. 

Holman RR. (1998) Assessing the potential for alpha-glucosidase inhibitors in prediabetic states. Diabetes Res Clin Pract 40 21-25. 

---