In Silico Docking Analysis of A-type Proanthocyanidins to <i>α</i>-Glucosidase Constructed by Correlation with in Vitro Bioassay

Sheau Ling Ho; Yili Lin; Shengfa Tsai; Shoeisheng Lee

doi:doi:10.11648/j.jddmc.20190504.11

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In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay

Sheau Ling Ho, Yili Lin, Shengfa Tsai, Shoeisheng Lee

Published in Journal of Drug Design and Medicinal Chemistry (Volume 5, Issue 4)

Received: 21 November 2019 Accepted: 7 December 2019 Published: 23 December 2019

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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.

Published in	Journal of Drug Design and Medicinal Chemistry (Volume 5, Issue 4)
DOI	10.11648/j.jddmc.20190504.11
Page(s)	47-60
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

α-Glucosidase, Proanthocyanidins, Bioassay, Molecular Docking, Proanthocyanidin Homologs, Peanut Skin

References

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APA Style

Sheau Ling Ho, Yili Lin, Shengfa Tsai, Shoeisheng Lee. (2019). 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, 5(4), 47-60. https://doi.org/10.11648/j.jddmc.20190504.11

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ACS Style

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. J. Drug Des. Med. Chem. 2019, 5(4), 47-60. doi: 10.11648/j.jddmc.20190504.11

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AMA Style

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. J Drug Des Med Chem. 2019;5(4):47-60. doi: 10.11648/j.jddmc.20190504.11

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@article{10.11648/j.jddmc.20190504.11,
  author = {Sheau Ling Ho and Yili Lin and Shengfa Tsai and Shoeisheng Lee},
  title = {In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {5},
  number = {4},
  pages = {47-60},
  doi = {10.11648/j.jddmc.20190504.11},
  url = {https://doi.org/10.11648/j.jddmc.20190504.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20190504.11},
  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.},
 year = {2019}
}

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TY  - JOUR
T1  - In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay
AU  - Sheau Ling Ho
AU  - Yili Lin
AU  - Shengfa Tsai
AU  - Shoeisheng Lee
Y1  - 2019/12/23
PY  - 2019
N1  - https://doi.org/10.11648/j.jddmc.20190504.11
DO  - 10.11648/j.jddmc.20190504.11
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 47
EP  - 60
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20190504.11
AB  - 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.
VL  - 5
IS  - 4
ER  -

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Author Information

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

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Plain Text BibTeX RIS

APA Style

Sheau Ling Ho, Yili Lin, Shengfa Tsai, Shoeisheng Lee. (2019). 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, 5(4), 47-60. https://doi.org/10.11648/j.jddmc.20190504.11

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ACS Style

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. J. Drug Des. Med. Chem. 2019, 5(4), 47-60. doi: 10.11648/j.jddmc.20190504.11

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AMA Style

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. J Drug Des Med Chem. 2019;5(4):47-60. doi: 10.11648/j.jddmc.20190504.11

Copy | Download

@article{10.11648/j.jddmc.20190504.11,
  author = {Sheau Ling Ho and Yili Lin and Shengfa Tsai and Shoeisheng Lee},
  title = {In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {5},
  number = {4},
  pages = {47-60},
  doi = {10.11648/j.jddmc.20190504.11},
  url = {https://doi.org/10.11648/j.jddmc.20190504.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20190504.11},
  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.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay
AU  - Sheau Ling Ho
AU  - Yili Lin
AU  - Shengfa Tsai
AU  - Shoeisheng Lee
Y1  - 2019/12/23
PY  - 2019
N1  - https://doi.org/10.11648/j.jddmc.20190504.11
DO  - 10.11648/j.jddmc.20190504.11
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 47
EP  - 60
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20190504.11
AB  - 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.
VL  - 5
IS  - 4
ER  -

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