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Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease
Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities by acting on multiple targets. Herein, nine coumarins from the root of Toddalia asiatica were evaluated for activities related to pathogenesis of Alzheimer’s disease (AD). They were examined for acetylcho...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277748/ https://www.ncbi.nlm.nih.gov/pubmed/32370238 http://dx.doi.org/10.3390/biomedicines8050107 |
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author | Takomthong, Pitchayakarn Waiwut, Pornthip Yenjai, Chavi Sripanidkulchai, Bungon Reubroycharoen, Prasert Lai, Ren Kamau, Peter Boonyarat, Chantana |
author_facet | Takomthong, Pitchayakarn Waiwut, Pornthip Yenjai, Chavi Sripanidkulchai, Bungon Reubroycharoen, Prasert Lai, Ren Kamau, Peter Boonyarat, Chantana |
author_sort | Takomthong, Pitchayakarn |
collection | PubMed |
description | Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities by acting on multiple targets. Herein, nine coumarins from the root of Toddalia asiatica were evaluated for activities related to pathogenesis of Alzheimer’s disease (AD). They were examined for acetylcholinesterase (AChE) and AChE- or self-induced amyloid beta (Aβ) aggregation inhibitory activities, as well as neuroprotection against H(2)O(2)- and Aβ(1–42)-induced human neuroblastoma SH-SY5Y cell damage. Moreover, in order to understand the mechanism, the binding interactions between coumarins and their targets: (i) AChE and (ii) Aβ(1–42) peptide were investigated in silico. All coumarins exhibited mild to moderate AChE and self-induced Aβ aggregation inhibitory actions. In addition, the coumarins substituted with the long alkyl chain at position 6 or 8 illustrated ability to inhibit AChE-induced Aβ aggregation, resulting from their dual binding site at catalytic anionic site and peripheral active site in AChE. Moreover, the most potent multifunctional coumarin, phellopterin, could attenuate neuronal cell damage induced by H(2)O(2) and Aβ(1–42) toxicity. Conclusively, seven out of nine coumarins were identified as multifunctional agents inhibiting the pathogenesis of AD. The structure–activity relationship information obtained might be applied for further optimization of coumarins into a useful drug which may combat AD. |
format | Online Article Text |
id | pubmed-7277748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72777482020-06-12 Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease Takomthong, Pitchayakarn Waiwut, Pornthip Yenjai, Chavi Sripanidkulchai, Bungon Reubroycharoen, Prasert Lai, Ren Kamau, Peter Boonyarat, Chantana Biomedicines Article Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities by acting on multiple targets. Herein, nine coumarins from the root of Toddalia asiatica were evaluated for activities related to pathogenesis of Alzheimer’s disease (AD). They were examined for acetylcholinesterase (AChE) and AChE- or self-induced amyloid beta (Aβ) aggregation inhibitory activities, as well as neuroprotection against H(2)O(2)- and Aβ(1–42)-induced human neuroblastoma SH-SY5Y cell damage. Moreover, in order to understand the mechanism, the binding interactions between coumarins and their targets: (i) AChE and (ii) Aβ(1–42) peptide were investigated in silico. All coumarins exhibited mild to moderate AChE and self-induced Aβ aggregation inhibitory actions. In addition, the coumarins substituted with the long alkyl chain at position 6 or 8 illustrated ability to inhibit AChE-induced Aβ aggregation, resulting from their dual binding site at catalytic anionic site and peripheral active site in AChE. Moreover, the most potent multifunctional coumarin, phellopterin, could attenuate neuronal cell damage induced by H(2)O(2) and Aβ(1–42) toxicity. Conclusively, seven out of nine coumarins were identified as multifunctional agents inhibiting the pathogenesis of AD. The structure–activity relationship information obtained might be applied for further optimization of coumarins into a useful drug which may combat AD. MDPI 2020-05-02 /pmc/articles/PMC7277748/ /pubmed/32370238 http://dx.doi.org/10.3390/biomedicines8050107 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Takomthong, Pitchayakarn Waiwut, Pornthip Yenjai, Chavi Sripanidkulchai, Bungon Reubroycharoen, Prasert Lai, Ren Kamau, Peter Boonyarat, Chantana Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease |
title | Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease |
title_full | Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease |
title_fullStr | Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease |
title_full_unstemmed | Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease |
title_short | Structure–Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer’s Disease |
title_sort | structure–activity analysis and molecular docking studies of coumarins from toddalia asiatica as multifunctional agents for alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277748/ https://www.ncbi.nlm.nih.gov/pubmed/32370238 http://dx.doi.org/10.3390/biomedicines8050107 |
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