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Exploring the Multitarget Activity of Wedelolactone against Alzheimer’s Disease: Insights from In Silico Study
[Image: see text] In this study, Wedelolactone’s multitarget activity against Alzheimer’s disease was examined using density functional theory and molecular docking techniques. At physiological pH, the pK(a) and molar fractions have been estimated. The most likely relative rate constants of two radi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157682/ https://www.ncbi.nlm.nih.gov/pubmed/37151498 http://dx.doi.org/10.1021/acsomega.2c08014 |
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author | Du, Dang Xuan Khang, Nguyen Huu Duy Tri, Nguyen Huu Nam, Pham Cam Thong, Nguyen Minh |
author_facet | Du, Dang Xuan Khang, Nguyen Huu Duy Tri, Nguyen Huu Nam, Pham Cam Thong, Nguyen Minh |
author_sort | Du, Dang Xuan |
collection | PubMed |
description | [Image: see text] In this study, Wedelolactone’s multitarget activity against Alzheimer’s disease was examined using density functional theory and molecular docking techniques. At physiological pH, the pK(a) and molar fractions have been estimated. The most likely relative rate constants of two radical scavenger mechanisms are formal hydrogen transfer in a lipid environment and single-electron transfer in a water solvent. Compared to Trolox (k(overall) = 8.96 × 10(4) M(–1) s(–1)), Wedelolactone (k(overall) = 4.26 × 10(9) M(–1) s(–1)) is more efficient in scavenging the HOO(•) radical in an aqueous environment. The chelation capacity of metals was investigated by examining the complexation of the Cu(II) ion at various coordination positions and calculating the complexation kinetic constants. Furthermore, molecular docking simulations showed that the known forms of Wedelolactone at physiological pH effectively inhibited the AChE and BChE enzymes by comparing their activity to that of tacrine (control). Wedelolactone is a promising drug candidate for Alzheimer’s disease therapy in light of these findings. |
format | Online Article Text |
id | pubmed-10157682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-101576822023-05-05 Exploring the Multitarget Activity of Wedelolactone against Alzheimer’s Disease: Insights from In Silico Study Du, Dang Xuan Khang, Nguyen Huu Duy Tri, Nguyen Huu Nam, Pham Cam Thong, Nguyen Minh ACS Omega [Image: see text] In this study, Wedelolactone’s multitarget activity against Alzheimer’s disease was examined using density functional theory and molecular docking techniques. At physiological pH, the pK(a) and molar fractions have been estimated. The most likely relative rate constants of two radical scavenger mechanisms are formal hydrogen transfer in a lipid environment and single-electron transfer in a water solvent. Compared to Trolox (k(overall) = 8.96 × 10(4) M(–1) s(–1)), Wedelolactone (k(overall) = 4.26 × 10(9) M(–1) s(–1)) is more efficient in scavenging the HOO(•) radical in an aqueous environment. The chelation capacity of metals was investigated by examining the complexation of the Cu(II) ion at various coordination positions and calculating the complexation kinetic constants. Furthermore, molecular docking simulations showed that the known forms of Wedelolactone at physiological pH effectively inhibited the AChE and BChE enzymes by comparing their activity to that of tacrine (control). Wedelolactone is a promising drug candidate for Alzheimer’s disease therapy in light of these findings. American Chemical Society 2023-04-18 /pmc/articles/PMC10157682/ /pubmed/37151498 http://dx.doi.org/10.1021/acsomega.2c08014 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Du, Dang Xuan Khang, Nguyen Huu Duy Tri, Nguyen Huu Nam, Pham Cam Thong, Nguyen Minh Exploring the Multitarget Activity of Wedelolactone against Alzheimer’s Disease: Insights from In Silico Study |
title | Exploring the Multitarget
Activity of Wedelolactone
against Alzheimer’s Disease: Insights from In Silico Study |
title_full | Exploring the Multitarget
Activity of Wedelolactone
against Alzheimer’s Disease: Insights from In Silico Study |
title_fullStr | Exploring the Multitarget
Activity of Wedelolactone
against Alzheimer’s Disease: Insights from In Silico Study |
title_full_unstemmed | Exploring the Multitarget
Activity of Wedelolactone
against Alzheimer’s Disease: Insights from In Silico Study |
title_short | Exploring the Multitarget
Activity of Wedelolactone
against Alzheimer’s Disease: Insights from In Silico Study |
title_sort | exploring the multitarget
activity of wedelolactone
against alzheimer’s disease: insights from in silico study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157682/ https://www.ncbi.nlm.nih.gov/pubmed/37151498 http://dx.doi.org/10.1021/acsomega.2c08014 |
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