Abstract
α-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit α-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an –OH group at 3′- and 4′- positions of B-ring and at 5- and 7- positions of A-ring and the C2 = C3 double bond, was the most active tested flavonoid, through competitive inhibition. In conclusion, some of the tested flavonoids have shown promising inhibition of α-amylase and may be considered as possible alternatives to the modulation of T2DM.
Highlights
A-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG)
The salivary isozyme provides an initial partial cleavage into shorter oligomers (10–30%)[7]. Once these partially digested saccharides reach the gut, they are extensively hydrolyzed by the a-amylase synthesized in the pancreas and excreted in the lumen into smaller oligosaccharides, such as maltose, maltotriose and a-limit dextrins (Figure 1)[3]. These sugars are broken down into glucose by the intestinal brush border a-glucosidases, which is in turn absorbed from the intestinal mucosa into the portal blood, by means of the glucose transporter (GLUT2) and sodium-glucose co-transporter 1 (SGLT1), leading to postprandial hyperglycaemia (PPHG)[2]
The tested flavonoids were divided into five groups (A–E), according to their substitution pattern
Summary
A-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). Introduction a-1,4-Glucan-4-glucanohydrolases (EC 3.2.1.1.), belonging to the family 13 of glycoside hydrolases (GH) and found in saliva and pancreatic juice, are known by the common name of a-amylase[1,2] Both are isozymes expressed respectively from genes AMY1 and AMY2 and are composed of 496 amino acid residues in a single polypeptide chain, presenting a 97% identity of the amino acids sequence and a 92% similarity of the residues in the catalytic domains[3–5]. The salivary isozyme provides an initial partial cleavage into shorter oligomers (10–30%)[7] Once these partially digested saccharides reach the gut, they are extensively hydrolyzed by the a-amylase synthesized in the pancreas and excreted in the lumen into smaller oligosaccharides, such as maltose, maltotriose and a-limit dextrins (Figure 1)[3]. The search and development of new effective and safer agents, able to control glucose levels is of high importance for the management of T2DM12
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