title: The search for novel human pancreatic alpha-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts.
abstract: Specific inhibitors of human pancreatic alpha-amylase (HPA) have potential as oral agents for the control of blood glucose levels in the treatment of diabetes and obesity. In a search for novel inhibitors, a library of 30 000 crude biological extracts of terrestrial and marine origin has been screened. A number of inhibitory extracts were identified, of which the most potent was subjected to bioassay-guided purification. A family of three glycosylated acyl flavonols, montbretins A-C, was thereby identified and characterized as competitive amylase inhibitors, with K(i) values ranging from 8.1-6100 nM. Competitive inhibition by myricetin, which corresponds to the flavone core, and noncompetitive inhibition by a second fragment, ethyl caffeiate, suggest a binding mode for these inhibitors.
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1Z1, Canada.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Tarling
authors.forename: Kate
authors.initials: K
authors.lastname: Woods
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Harry C
authors.initials: HC
authors.lastname: Brastianos
authors.forename: Gary D
authors.initials: GD
authors.lastname: Brayer
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Andersen
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D010179:Pancreas / Q000201:enzymology*; D000516:alpha-Amylases / Q000037:antagonists & inhibitors*
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D000516:alpha-Amylases