Coumarin compounds against Alzheimer's disease: An in-silico approach
Alzheimer's disease, one of the most common causes of senile dementia, has no cure which makes the development of new treatments crucial. In this regard, secondary metabolites from plants have shown important bioactivity, including the inhibitory effect against acetylcholinesterase enzyme (AChE...
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Elsevier
2025-07-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625004643 |
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| author | Mayra Avelar Patricia Fernanda Delgado-Acosta Ricardo Guzmán-Ávila Virginia Flores-Morales |
| author_facet | Mayra Avelar Patricia Fernanda Delgado-Acosta Ricardo Guzmán-Ávila Virginia Flores-Morales |
| author_sort | Mayra Avelar |
| collection | DOAJ |
| description | Alzheimer's disease, one of the most common causes of senile dementia, has no cure which makes the development of new treatments crucial. In this regard, secondary metabolites from plants have shown important bioactivity, including the inhibitory effect against acetylcholinesterase enzyme (AChE). An important group of such metabolites are coumarins, in particular the 7-hydroxycoumarin and its derivatives. These molecules have a wide variety of biological activities as antioxidants, anti-neurodegenerative and anti-Alzheimer drugs. In this study, eight coumarin derivatives were analyzed by means of ADMET properties, molecular docking and molecular dynamics simulations. Out of our set of derivatives, four coumarin compounds showed better docking scores (–11.60 to –12.07 kcal/mol) than the reference molecule donepezil, one of the drugs of first-line in the treatment of the disease as a reversible inhibitor of AChE. According to molecular dynamics simulations, the top selected compounds (Cou2, Cou5, Cou6 and Cou8) displayed interactions with amino acids from the binding site of AChE as potential multisite inhibitors, maintaining its interaction during the simulation time. The studied coumarins showed a biological activity as anti-inflammatory and free radical scavenger, regarding in silico predictions. All coumarins had good physicochemical and pharmacokinetic predicted parameters, thus positioned them as potential candidates to prove as Alzheimer's disease drugs by in vitro and in vivo evaluations. |
| format | Article |
| id | doaj-art-971c7c8ea65e401abc36799e29398824 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Results in Chemistry |
| spelling | doaj-art-971c7c8ea65e401abc36799e293988242025-08-20T03:43:54ZengElsevierResults in Chemistry2211-71562025-07-011610248110.1016/j.rechem.2025.102481Coumarin compounds against Alzheimer's disease: An in-silico approachMayra Avelar0Patricia Fernanda Delgado-Acosta1Ricardo Guzmán-Ávila2Virginia Flores-Morales3Laboratorio de Síntesis Asimétrica y Bio-Quimioinformática (LSAyB), Ingeniería Química (UACQ), Universidad Autónoma de Zacatecas, Campus XXI Km 6 Carr. Zac-Gdl, Zacatecas 98160, Mexico; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy; Corresponding authors.Laboratorio de Síntesis Asimétrica y Bio-Quimioinformática (LSAyB), Ingeniería Química (UACQ), Universidad Autónoma de Zacatecas, Campus XXI Km 6 Carr. Zac-Gdl, Zacatecas 98160, MexicoLaboratorio de Síntesis Asimétrica y Bio-Quimioinformática (LSAyB), Ingeniería Química (UACQ), Universidad Autónoma de Zacatecas, Campus XXI Km 6 Carr. Zac-Gdl, Zacatecas 98160, MexicoLaboratorio de Síntesis Asimétrica y Bio-Quimioinformática (LSAyB), Ingeniería Química (UACQ), Universidad Autónoma de Zacatecas, Campus XXI Km 6 Carr. Zac-Gdl, Zacatecas 98160, Mexico; Corresponding authors.Alzheimer's disease, one of the most common causes of senile dementia, has no cure which makes the development of new treatments crucial. In this regard, secondary metabolites from plants have shown important bioactivity, including the inhibitory effect against acetylcholinesterase enzyme (AChE). An important group of such metabolites are coumarins, in particular the 7-hydroxycoumarin and its derivatives. These molecules have a wide variety of biological activities as antioxidants, anti-neurodegenerative and anti-Alzheimer drugs. In this study, eight coumarin derivatives were analyzed by means of ADMET properties, molecular docking and molecular dynamics simulations. Out of our set of derivatives, four coumarin compounds showed better docking scores (–11.60 to –12.07 kcal/mol) than the reference molecule donepezil, one of the drugs of first-line in the treatment of the disease as a reversible inhibitor of AChE. According to molecular dynamics simulations, the top selected compounds (Cou2, Cou5, Cou6 and Cou8) displayed interactions with amino acids from the binding site of AChE as potential multisite inhibitors, maintaining its interaction during the simulation time. The studied coumarins showed a biological activity as anti-inflammatory and free radical scavenger, regarding in silico predictions. All coumarins had good physicochemical and pharmacokinetic predicted parameters, thus positioned them as potential candidates to prove as Alzheimer's disease drugs by in vitro and in vivo evaluations.http://www.sciencedirect.com/science/article/pii/S2211715625004643Alzheimer's diseaseCoumarin compoundsMolecular dockingMolecular dynamicsADMET |
| spellingShingle | Mayra Avelar Patricia Fernanda Delgado-Acosta Ricardo Guzmán-Ávila Virginia Flores-Morales Coumarin compounds against Alzheimer's disease: An in-silico approach Results in Chemistry Alzheimer's disease Coumarin compounds Molecular docking Molecular dynamics ADMET |
| title | Coumarin compounds against Alzheimer's disease: An in-silico approach |
| title_full | Coumarin compounds against Alzheimer's disease: An in-silico approach |
| title_fullStr | Coumarin compounds against Alzheimer's disease: An in-silico approach |
| title_full_unstemmed | Coumarin compounds against Alzheimer's disease: An in-silico approach |
| title_short | Coumarin compounds against Alzheimer's disease: An in-silico approach |
| title_sort | coumarin compounds against alzheimer s disease an in silico approach |
| topic | Alzheimer's disease Coumarin compounds Molecular docking Molecular dynamics ADMET |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625004643 |
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