Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors.
Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a seri...
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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.0317261 |
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| author | Fatima Zahra Guerguer Bouchra Rossafi Oussama Abchir Yasir S Raouf Dhabya Bakhit Albalushi Abdelouahid Samadi Samir Chtita |
| author_facet | Fatima Zahra Guerguer Bouchra Rossafi Oussama Abchir Yasir S Raouf Dhabya Bakhit Albalushi Abdelouahid Samadi Samir Chtita |
| author_sort | Fatima Zahra Guerguer |
| collection | DOAJ |
| description | Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest. Out of the 63 Azo-8HQ derivatives analysed, two molecules, 14c and 17c, demonstrated strong affinities for AChE, BuChE, and MAO-B, along with favourable pharmacokinetic profiles and electronic properties. Molecular dynamics simulations confirmed the stability of these molecules within the active sites of the targets, and MM-GBSA calculations revealed low binding energies, indicating robust interactions. These findings identify molecules 14c and 17c as promising multi-target candidates for the treatment of AD, based on an in-depth computational study aimed at minimizing drug development costs and time. Future work will include the synthesis of these molecules followed by in-depth in vitro and in vivo testing to validate their potential therapeutic efficacy. |
| format | Article |
| id | doaj-art-6163761bbb0040e094eca5677499920f |
| 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-6163761bbb0040e094eca5677499920f2025-02-07T05:30:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031726110.1371/journal.pone.0317261Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors.Fatima Zahra GuerguerBouchra RossafiOussama AbchirYasir S RaoufDhabya Bakhit AlbalushiAbdelouahid SamadiSamir ChtitaCognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest. Out of the 63 Azo-8HQ derivatives analysed, two molecules, 14c and 17c, demonstrated strong affinities for AChE, BuChE, and MAO-B, along with favourable pharmacokinetic profiles and electronic properties. Molecular dynamics simulations confirmed the stability of these molecules within the active sites of the targets, and MM-GBSA calculations revealed low binding energies, indicating robust interactions. These findings identify molecules 14c and 17c as promising multi-target candidates for the treatment of AD, based on an in-depth computational study aimed at minimizing drug development costs and time. Future work will include the synthesis of these molecules followed by in-depth in vitro and in vivo testing to validate their potential therapeutic efficacy.https://doi.org/10.1371/journal.pone.0317261 |
| spellingShingle | Fatima Zahra Guerguer Bouchra Rossafi Oussama Abchir Yasir S Raouf Dhabya Bakhit Albalushi Abdelouahid Samadi Samir Chtita Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors. PLoS ONE |
| title | Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors. |
| title_full | Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors. |
| title_fullStr | Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors. |
| title_full_unstemmed | Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors. |
| title_short | Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors. |
| title_sort | potential azo 8 hydroxyquinoline derivatives as multi target lead candidates for alzheimer s disease an in depth in silico study of monoamine oxidase and cholinesterase inhibitors |
| url | https://doi.org/10.1371/journal.pone.0317261 |
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