Deciphering the Inactivation of Human Pancreatic α-Amylase, an Antidiabetic Target, by Bisdemethoxycurcumin, a Small Molecule Inhibitor, Isolated from Curcuma longa
Natural products from plants are an excellent source of Human pancreatic α-amylase (HPA) inhibitors which have therapeutic application as oral agents to control blood glucose levels. The mechanism of action by Bisdemethoxycurcumin (BDMC) has been reported, isolated from Curcuma
longa rhizomes, which inactivates HPA, a target for type-2 diabetes. This study validates its mode of action and its target which has to date remained largely unknown. The cytotoxicity and bioactivity of crude extract and BDMC on the pancreatic acinar AR42J secretory model cell line were evaluated
with LD50 value of 16.25 μg ml-1 and 63.53 μM, and secretory α-amylase inhibition of 41% and 30%, respectively. BDMC uncompetitively inhibits HPA (Ki' of 10.1μM) and a binding affinity (Ka) of 8.5 x 104 M-1 with the involvement of surface exposed aromatic
residues. The thermodynamic parameters suggest that binding is both enthalpically and entropically driven with ΔGº of - 28.13 kJ mol-1. Computational ligand docking showed that inactivation depends on hydrogen bonding and π-π interactions. Thus, BDMC, a natural product could
be lowering post-prandial glycemia via a novel mode of binding and inactivation of HPA and may proved to be a good drug candidate to reduce/control post-prandial hyperglycemia.
Keywords: AR42J cell line; Human pancreatic α-amylase; bisdemethoxycurcumin; docking; ligand binding
Document Type: Research Article
Publication date: 01 March 2013
The Natural Products Journal, a peer reviewed journal, aims to publish all the latest and outstanding developments in natural products.
The Natural Products Journal publishes original research articles, reviews, letters and guest edited issues on all aspects of research and development in the field including: isolation, purification, structure elucidation, synthesis and bioactivity of chemical compounds found in nature.
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