α-amylase is an important target for the maintenance of postprandial blood glucose level, especially for patients with diabetes. Currently, the available drug acarbose has disturbing gastrointestinal side-effects that cannot be neglected. Thus, development of novel α-amylase inhibitors with no side-effects as functional food is of great importance. Natural products have been widely recognized as a promising source for discovery of bioactive components. Here, we adopt a computer-aided approach to search for potential α-amylase inhibitors in a natural product database. Virtual screening was first used to assess every compound in the database, then the results were ranked on the basis of predicted binding energy. The top 1% ranked compounds were selected as candidate compounds and evaluated in <i>in vitro</i> enzymatic activity and kinetic assays. The compound with the best inhibitory activity was evaluated with CD spectroscopy and oral starch tolerance test in mice and identified as a novel α-amylase inhibitor. Molecular docking and molecular dynamics were subsequently used to identify the inhibitory mechanism. Then pharmacophore modeling and 3D-QSAR analyses were used in combination to generate a model for computer-aided design of α-amylase inhibitors. Taken together, our results offer new insights for discovery of novel α-amylase inhibitors as functional food from natural products, for control of postprandial blood glucose level.

Discovery of novel α-amylase inhibitors from natural products with a computer-aided approach

2019 Fall National Meeting

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