title: α-Glucosidase-inhibitory iminosugars from the leaves of Suregada glomerulata.
abstract: A water extract of the leaves of Suregada glomerulata (Euphorbiaceae) was found to inhibit rat small intestinal α-glucosidase. An examination of the extract afforded 20 iminosugars including one pyrrolidine and 19 piperidines. The structures of the 10 new compounds (11-20) were determined by NMR, and MS spectroscopic data analyses, and chemical correlations. The novelty of the identified compounds mainly stems from the loss of a hydroxy at C-4 and the presence of an 8-hydroxyoctyl side chain. Nine N-alkyl derivatives including N-methyl (1a, 8a, and 13a), N-butyl (1b, 2b, and 9b) and N,N-dimethyl (1c, 2c, and 9c) were synthesized. The compounds were tested for rat small intestinal α-glucosidase inhibitory activity. In total, 15 compounds, including compounds 11, 12, 15, and 19 and the three derivatives 8a, 9b, and 13a, showed inhibitory activity with IC50 values less than 40μM. In vivo results showed that total alkaloids of S. glomerulata (10mg/kg) and four major iminosugars 1, 2, 3, and 9 (10mg/kg) can lower the postprandial blood glucose level after sucrose and starch load in healthy male ICR mice.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
authors.forename: Ren-Yi
authors.initials: RY
authors.lastname: Yan
authors.forename: Hong-Qing
authors.initials: HQ
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Kang
authors.forename: Ruo-Yun
authors.initials: RY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D065089:Glycoside Hydrolase Inhibitors; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D050111:Imino Sugars / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D007421:Intestine, Small / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008968:Molecular Conformation; D018515:Plant Leaves / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D029843:Suregada / Q000737:chemistry* / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D050111:Imino Sugars; D000520:alpha-Glucosidases
keywords: Euphorbiaceae; Iminosugar; Piperidine; Pyrrolidine; Suregada glomerulata; α-Glucosidase inhibitory activity