Journal of Drug Design and Medicinal Chemistry

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

Received: 21 November 2019    Accepted: 07 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.

DOI 10.11648/j.jddmc.20190504.11
Published in Journal of Drug Design and Medicinal Chemistry (Volume 5, Issue 4, December 2019)
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), 2024. Published by Science Publishing Group

Keywords

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

References
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[14] Sim, L., K. Jayakanthan, S. Mohan, R. Nasi, B. D. Johnston, B. M. Pinto, and D. R. Rose (2010) New glucosidase inhibitors from an Ayurvedic herbal treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata. Biochemistry 49, 443−451.
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Author Information
  • Department of Chemical & Materials Engineering, Chinese Culture University, Taipei, Taiwan, ROC

  • School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

  • School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

  • School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

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    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://download.sciencepg.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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