The search for novel human pancreatic alpha-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts.
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.
Tarling
Chris A
CA
Department of Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1Z1, Canada.
Woods
Kate
K
Zhang
Ran
R
Brastianos
Harry C
HC
Brayer
Gary D
GD
Andersen
Raymond J
RJ
Withers
Stephen G
SG
D001688:Biological Products / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D010179:Pancreas / Q000201:enzymology*; D000516:alpha-Amylases / Q000037:antagonists & inhibitors*
D001688:Biological Products; D004791:Enzyme Inhibitors; D000516:alpha-Amylases