- Poster presentation
- Open Access
Discovery of novel α-amylase inhibitors using structure-based drug design
Journal of Cheminformatics volume 6, Article number: P50 (2014)
α-Amylase is an endoamylase and belongs to glycoside hydrolase family 13 (GH 13) according to the classification of carbohydrate-active enzymes . It initiates starch hydrolysis into smaller oligomers. Inhibitors of this enzyme are of pharmacological importance as α-amylase is considered as attractive target for treating elevated post-prandial blood glucose levels resulting in obesity and type II diabetes. Besides the application as a drug, it is highly interesting to classify nutritional components, such as food additives or secondary plant metabolites with respect to their modulation of α-amylase.
We present a model that predicts the affinity of small organic molecules to α- amylase. On the basis of available crystal structures (Figure 1) , we developed a virtual screening workflow for the identification of novel non- peptidic, non-carbohydrate α-amylase inhibitors. In addition to virtual screening using structure-based 3D pharmacophore models , molecular docking and clustering for diversity selection have been applied as post-screening filters. Fourteen virtual hits were purchased and tested in vitro using a kinetic assay with p-Nitrophenyl-α-d-maltopentaoside (PNPG5) as a chromogenic substrate. Three of those fourteen compounds showed concentration-dependent inhibition with promising IC50 values (hit rate: 21%).
Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B: The carbohydrate-active enzymes database (cazy): An expert resource for glycogenomics. Nucleic Acids Res. 2009, 37: D233-D238. 10.1093/nar/gkn663.
Qin X, Ren L, Yang X, Bai F, Wang L, Geng P, Bai G, Shen Y: Structures of human pancreatic alpha-amylase in complex with acarviostatins: Implications for drug design against type II diabetes. J Struct Biol. 2011, 174 (1): 196-202. 10.1016/j.jsb.2010.11.020.
Wolber G, Langer T: Ligandscout: 3-d pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model. 2005, 45 (1): 160-169. 10.1021/ci049885e.
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Al-Asri, J., Wolber, G. Discovery of novel α-amylase inhibitors using structure-based drug design. J Cheminform 6 (Suppl 1), P50 (2014). https://doi.org/10.1186/1758-2946-6-S1-P50
- Molecular Docking
- Virtual Screening
- Pharmacophore Model
- Secondary Plant Metabolite
- Glycoside Hydrolase Family