Volume 5, Issue 4, December 2019, Page: 47-60
In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay
Sheau Ling Ho, Department of Chemical & Materials Engineering, Chinese Culture University, Taipei, Taiwan, ROC
Yili Lin, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
Shengfa Tsai, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
Shoeisheng Lee, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
Received: Nov. 21, 2019;       Accepted: Dec. 7, 2019;       Published: Dec. 23, 2019
DOI: 10.11648/j.jddmc.20190504.11      View  365      Downloads  113
Abstract
The type A proanthocyanidins (2−8) with (2β→O→7, 4β→8) interflavane linkage, isolated from Machilus philippinensis, have been found to possess inhibitory activity against α-glucosidase (EC 3.2.1.20 from Bacillus stearothermophilus). To rationalize such activity, computer assisted docking of these compounds and the positive control, acarbose, on the conformation model of α-glucosidase (AG), built by using human intestinal maltase glucoamylase as a template, was undertaken in this study. The result showed good correlation between IC50 values and docking scores, expressed as binding energy (ΔG), obtained from London (trimatch)-refinement (forcefield AffinityΔG) mode. Among these isolates, the most potent aesculitannin B (2) (IC50 3.5μM) showed the best docking score (ΔG -21.48 kcal/mol). Being interested in clarification of structure and activity relationship, virtual screening on the related compounds, including the de-unit III homologs of 2−8 (i.e., nor- series) and additional 13 stereoisomers of the trimeric 2 at the C-2 and C-3 positions of units II and III, was further carried out. This docking study indicated the de-unit III homologs of 2−8 did not have better binding energies than 2. As for the trimers, 3-entC, 3C-entE, 3ent-C, 3C, and 3ent, showed comparable docking score to 2. The verification of this virtual screening was partially done by evaluating the inhibitory activity of the dimeric 2-nor-ent, 3-nor, 3-nor-ent, and iso-2-nor-ent, isolated from peanut skins, against α-glucosidase. Of these, iso-2-nor-ent, the only proanthocyanidin with (2β→O→7, 4β→6) interflavane linkage, showed the best activity (IC50 9.72 μM). Their simulation profiles of docking score also displayed a reasonable qualitative consistency with the overall trend of the bioassay results. This study demonstrates that virtual screening using this built model to search α-glucosidase inhibitors is facile and feasible and peanut skin might be used as a hypoglycemic food.
Keywords
α-Glucosidase, Proanthocyanidins, Bioassay, Molecular Docking, Proanthocyanidin Homologs, Peanut Skin
To cite this article
Sheau Ling Ho, Yili Lin, Shengfa Tsai, Shoeisheng Lee, In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay, Journal of Drug Design and Medicinal Chemistry. Vol. 5, No. 4, 2019, pp. 47-60. doi: 10.11648/j.jddmc.20190504.11
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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