Synthesis of Montbretin A Analogues Yields Potent Competitive Inhibitors of Human Pancreatic α-Amylase

Simplified analogues of the potent human amylase inhibitor Montbretin A were synthesised and shown to bind tightly, Ki = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed similar binding modes and identified new active site interactions.