Synthesis of novel triterpene and N-allylated/N-alkylated niacin hybrids as α-glucosidase inhibitors

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. α-Glucosidase (EC 3.2.1.20) inhibitors interfere with enzymatic action to slow down the liberation of d-glucose from oligosaccharides and disaccharides, resulting in delayed glucose absorption and decreased postprandial plasma glucose levels. In continuation of our drug discovery program on antidiabetic agents, we synthesized novel N-allylated/N-alkylated niacin and α-amyrin (4–9) and lupeol (12–16) hybrids and tested for their α-glucosidase inhibiting activity. Compounds 4–9 showed better activity profile than the marketed α-glucosidase inhibitor i.e. acarbose. Compound 4 possess the highest inhibitory action with IC50 of 5 μM. Kinetic and CD studies revealed that 4 inhibited the α-glucosidase in a noncompetitive manner and caused conformational changes in secondary structure of the enzyme protein.

Graphical abstractNovel N-allylated/N-alkylated niacin and α-amyrin (4–9) and lupeol (12–16) hybrids were synthesized and tested for α-glucosidase inhibiting activity. Compounds 4–9 showed better activity profile than the marketed α-glucosidase inhibitor i.e. acarbose.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel N-allylated and N-alkylated salts of triterpenes and niacin hybrids were synthesized. ► Their α-glucosidase inhibitory action was tested. ► Compound 4 is ten times more potent than acarbose. ► Compound 4 showed 19.9% reduction in blood glucose level at 100 mg/kg dose level in sucrose-loaded STZ-induced diabetic rats.