Synthesis and kinetics studies of N′‐(2‐(3,5‐disubstituted‐4H‐1,2,4‐triazol‐4‐yl)acetyl)‐6/7/8‐substituted‐2‐oxo‐2H‐chromen‐3‐carbohydrazide derivatives as potent antidiabetic agents

Abstract

A novel series of N′‐(2‐(3,5‐disubstituted‐4H‐1,2,4‐triazol‐4‐yl)acetyl)‐6/7/8‐substituted‐2‐oxo‐2H‐chromen‐3‐carbohydrazides were synthesized and studied for their α‐glucosidase inhibition activity. Most of the synthesized compounds exhibited potential α‐glucosidase inhibition activity with IC50 values ranging from 0.96 ± 0.02 to 32.86 ± 0.73 µg/ml. Among them, compounds 3e and 4e, having a methoxy group on the coumarin ring, proved to be the most potent ones, showing an enzyme inhibition activity with IC50 = 0.96 ± 0.02 and 1.44 ± 0.06 µg/ml, respectively. The kinetic study through Lineweaver–Burk plots revealed that the inhibition mechanism of the most active compounds 3d, 3e, 4d, and 4e, on the α‐glucosidase activity, was found to be in the competitive mode.

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

“…Diabetes is a chronic metabolic disease characterized by high blood sugar levels and is generally caused by an insufficient production of insulin by β-pancreatic cells or by the inability of human body to use this hormone. The consequences of diabetes might be very serious: blindness, kidney failure, stroke, heart attacks, lower limb amputation [204][205][206] Menteşe et al synthesized a novel series of N'-(2-(3,5-disubstituted-4H-1,2,4-triazol-4-yl)acetyl)-6/7/8 substituted-2-oxo-2H-chromen-3-carbohydrazides (158a-e, 159a-e, Figure 54) [207], merging the 1,2,4-triazole and the coumarin moieties, both characterized by a wide range of biological activities (including inhibition of α-glucosidases) and low toxicity profiles [208][209][210][211][212][213]. Then, their activity on α-glucosidases was studied, evaluating the enzyme inhibition in the presence of pNPG Compounds 158e and 159e resulted the most active, probably because of the metoxy-group at position 8 of the coumarin ring.…”

One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors

“…With the help of the bloodstream, these simple sugars enter the cells and are converted into energy with the help of insulin. Without insulin (inadequate insulin secretion or insulin resistance), glucose stays in the bloodstream, keeping blood sugar levels high which leads to hyperglycemia, impaired glucose tolerance, and at late-stage type II diabetes [ 11 – 13 ].…”

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

“…It hydrolyzes oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides at their non-reducing ends (α-glycosidic bonds) after hydrolysis of polysaccharides to oligosaccharides by α-amylase. As a result, α-glycosidase inhibitors transfer the undigested carbohydrate into the distal part of the small intestine and colon, delay the process of carbohydrate absorption in the gastrointestinal tract, and reduce postprandial hyperglycemia [ 4 , 11 , 12 ].…”