Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study.
Alzheimer's disease is a neurodegenerative disorder that impairs neurocognitive functions. Acetylcholinesterase, Butyrylcholinesterase, Monoamine Oxidase B, Beta-Secretase, and Glycogen Synthase Kinase Beta play central roles in its pathogenesis. Current medications primarily inhibit AChE but f...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0313411 |
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| author | Fatima Zahra Guerguer Amal Bouribab El Mehdi Karim Meriem Khedraoui Fatiha Amegrissi Yasir S Raouf Abdelouahid Samadi Samir Chtita |
| author_facet | Fatima Zahra Guerguer Amal Bouribab El Mehdi Karim Meriem Khedraoui Fatiha Amegrissi Yasir S Raouf Abdelouahid Samadi Samir Chtita |
| author_sort | Fatima Zahra Guerguer |
| collection | DOAJ |
| description | Alzheimer's disease is a neurodegenerative disorder that impairs neurocognitive functions. Acetylcholinesterase, Butyrylcholinesterase, Monoamine Oxidase B, Beta-Secretase, and Glycogen Synthase Kinase Beta play central roles in its pathogenesis. Current medications primarily inhibit AChE but fail to halt or reverse disease progression due to the multifactorial nature of Alzheimer's. This underscores the necessity of developing multi-target ligands for effective treatment. This study investigates the potential of phytochemical compounds from Moroccan medicinal plants as multi-target agents against Alzheimer's disease, employing computational approaches. A virtual screening of 386 phytochemical compounds, followed by an assessment of pharmacokinetic properties and ADMET profiles, led to the identification of two promising compounds, naringenin (C23) and hesperetin (C24), derived from Anabasis aretioides. These compounds exhibit favourable pharmacokinetic profiles and strong binding affinities for the five key targets associated with the disease. Density functional theory, molecular dynamics simulations, and MM-GBSA calculations further confirmed their structural stability, with a slight preference for C24, exhibiting superior intermolecular interactions and overall stability. These findings provide a strong basis for further experimental research, including in vitro and in vivo studies, to substantiate their potential efficacy in Alzheimer's disease. |
| format | Article |
| id | doaj-art-cecaeb24dcb34162a01d6a3a2b0045d2 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-cecaeb24dcb34162a01d6a3a2b0045d22025-02-05T05:31:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031341110.1371/journal.pone.0313411Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study.Fatima Zahra GuerguerAmal BouribabEl Mehdi KarimMeriem KhedraouiFatiha AmegrissiYasir S RaoufAbdelouahid SamadiSamir ChtitaAlzheimer's disease is a neurodegenerative disorder that impairs neurocognitive functions. Acetylcholinesterase, Butyrylcholinesterase, Monoamine Oxidase B, Beta-Secretase, and Glycogen Synthase Kinase Beta play central roles in its pathogenesis. Current medications primarily inhibit AChE but fail to halt or reverse disease progression due to the multifactorial nature of Alzheimer's. This underscores the necessity of developing multi-target ligands for effective treatment. This study investigates the potential of phytochemical compounds from Moroccan medicinal plants as multi-target agents against Alzheimer's disease, employing computational approaches. A virtual screening of 386 phytochemical compounds, followed by an assessment of pharmacokinetic properties and ADMET profiles, led to the identification of two promising compounds, naringenin (C23) and hesperetin (C24), derived from Anabasis aretioides. These compounds exhibit favourable pharmacokinetic profiles and strong binding affinities for the five key targets associated with the disease. Density functional theory, molecular dynamics simulations, and MM-GBSA calculations further confirmed their structural stability, with a slight preference for C24, exhibiting superior intermolecular interactions and overall stability. These findings provide a strong basis for further experimental research, including in vitro and in vivo studies, to substantiate their potential efficacy in Alzheimer's disease.https://doi.org/10.1371/journal.pone.0313411 |
| spellingShingle | Fatima Zahra Guerguer Amal Bouribab El Mehdi Karim Meriem Khedraoui Fatiha Amegrissi Yasir S Raouf Abdelouahid Samadi Samir Chtita Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study. PLoS ONE |
| title | Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study. |
| title_full | Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study. |
| title_fullStr | Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study. |
| title_full_unstemmed | Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study. |
| title_short | Moroccan natural products for multitarget-based treatment of Alzheimer's disease: A computational study. |
| title_sort | moroccan natural products for multitarget based treatment of alzheimer s disease a computational study |
| url | https://doi.org/10.1371/journal.pone.0313411 |
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