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. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Citation

Tadigoppula Narender, Gaurav Madhur, Natasha Jaiswal, Manali Agrawal, Chandan K Maurya, Neha Rahuja, Arvind K Srivastava, Akhilesh K Tamrakar. Synthesis of novel triterpene and N-allylated/N-alkylated niacin hybrids as α-glucosidase inhibitors. European journal of medicinal chemistry. 2013 May;63:162-9

PMID: 23474902

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