The search for novel human pancreatic α-amylase inhibitors:: High-throughput screening of terrestrial and marine natural product extracts

Specific inhibitors of human pancreatic a-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 30000 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 1 bioassay-guided purification. A family of three glycosylated acyl flavonols, montbretins A-C-1 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.