In silico evaluation of condensed and hydrolysable tannins as inhibitors of pancreatic α-amylase
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Amylases are interesting targets for antidiabetic drugs because their inhibition is able to lower glycaemia without the need of hormonal control, as promoted by insulin or glibenclamide. In this context, the comparison between the binding features of α-amylases with their substrate and known inhibitors may provide insights aiming at the discovery of new antidiabetic drugs. In this work, the structure of the porcine pancreatic α-amylase was modelled with the acarbose pentasaccharide inhibitor, and used in structure-based virtual screening simulations based on a library containing the structures of amylose (AMY), acarbose (ACA) and the more representative structures of condensed tannin (CTN) and hydrolysable tannin (HTN). After validation of the methodology by redocking (mean rmsd ~ 0.8 Å), the scores provided by programs AutoDock/Molegro were contradictory (− 1.5/− 23.3; − 3.5/− 24.6; − 4.3/− 14.6; −/− 19.5 for AMY, ACA, CTN and HTN respectively), indicating that a more sensitive methodology was necessary. The ΔGbinding was calculated by the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method, which indicated that the HTN, ACA and CTN had higher affinities for the enzyme regarding the AMY substrate, with values of − 350.0, − 346.2, − 320.5 and − 209.2 kJ mol−1, respectively. The predicted relative affinities of HTN and CTN are in agreement with those obtained experimentally. The results provided useful information for the characterization of tannin binding to α-amylase, which can be applied in future studies aiming at finding new hypoglycaemic molecules among natural products.
KeywordsEnzyme Diabetes Natural products MM-PBSA Docking
The authors would like to acknowledge LNCC for computational facilities.
This work was financially supported by Fundação Araucária (grant numbers 147/14 and 40/16), Coordination for the Improvement of Higher Education Personnel–Brazil (CAPES, cód 001) and National Council for Scientific and Technological Development–Brazil (CNPq grant number 305960/2015-6); CENAPAD/SP (Project number 520).
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