title: Synthesis of novel triterpene and N-allylated/N-alkylated niacin hybrids as α-glucosidase inhibitors.
abstract: 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.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India. t_narendra@cdri.res.in
authors.forename: Tadigoppula
authors.initials: T
authors.lastname: Narender
authors.forename: Gaurav
authors.initials: G
authors.lastname: Madhur
authors.forename: Natasha
authors.initials: N
authors.lastname: Jaiswal
authors.forename: Manali
authors.initials: M
authors.lastname: Agrawal
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Maurya
authors.forename: Neha
authors.initials: N
authors.lastname: Rahuja
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Tamrakar
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009525:Niacin / Q000737:chemistry*; D051381:Rats; D016896:Treatment Outcome; D014315:Triterpenes / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D014315:Triterpenes; D009525:Niacin; D000520:alpha-Glucosidases