A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study
Cholinesterases are enzymes that break down the neurotransmitter acetylcholine in the nervous system. The two main types are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). AChE inhibitors are used to treat Alzheimer’s disease by increasing acetylcholine levels. BChE activity increases...
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MDPI AG
2024-12-01
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| author | Evdokiya Salamanova Mariyana Atanasova Irini Doytchinova |
| author_facet | Evdokiya Salamanova Mariyana Atanasova Irini Doytchinova |
| author_sort | Evdokiya Salamanova |
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| description | Cholinesterases are enzymes that break down the neurotransmitter acetylcholine in the nervous system. The two main types are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). AChE inhibitors are used to treat Alzheimer’s disease by increasing acetylcholine levels. BChE activity increases in later stages of Alzheimer’s, suggesting it might contribute to the disease. In previous experiments, it was found that a newly designed hybrid of galantamine (GAL) and curcumin (CCN) (compound <b>4b</b>) decreases the activity of BChE in murine brain homogenates. Here, we explore this observation using molecular dynamics simulations. GAL and CCN were also studied for comparison. The structures of the complexes between the BChE and the ligands were predicted by molecular docking. Then, molecular dynamics simulations were performed to evaluate the stability of the complexes and the interactions between the ligands and the enzyme over a simulated time of 1 μs. All three ligands formed stable complexes with BChE. Compound <b>4b</b> formed more hydrogen bonds and other interactions with BChE compared to GAL and CCN, suggesting a stronger binding affinity. The stronger binding of <b>4b</b> to BChE might explain its superior anti-BChE activity observed in previous experiments. |
| format | Article |
| id | doaj-art-932b625dd7854a4e8fa35a3e10e0dc7d |
| institution | Kabale University |
| issn | 2624-8549 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Chemistry |
| spelling | doaj-art-932b625dd7854a4e8fa35a3e10e0dc7d2024-12-27T14:17:01ZengMDPI AGChemistry2624-85492024-12-01661645165710.3390/chemistry6060100A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics StudyEvdokiya Salamanova0Mariyana Atanasova1Irini Doytchinova2Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaCholinesterases are enzymes that break down the neurotransmitter acetylcholine in the nervous system. The two main types are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). AChE inhibitors are used to treat Alzheimer’s disease by increasing acetylcholine levels. BChE activity increases in later stages of Alzheimer’s, suggesting it might contribute to the disease. In previous experiments, it was found that a newly designed hybrid of galantamine (GAL) and curcumin (CCN) (compound <b>4b</b>) decreases the activity of BChE in murine brain homogenates. Here, we explore this observation using molecular dynamics simulations. GAL and CCN were also studied for comparison. The structures of the complexes between the BChE and the ligands were predicted by molecular docking. Then, molecular dynamics simulations were performed to evaluate the stability of the complexes and the interactions between the ligands and the enzyme over a simulated time of 1 μs. All three ligands formed stable complexes with BChE. Compound <b>4b</b> formed more hydrogen bonds and other interactions with BChE compared to GAL and CCN, suggesting a stronger binding affinity. The stronger binding of <b>4b</b> to BChE might explain its superior anti-BChE activity observed in previous experiments.https://www.mdpi.com/2624-8549/6/6/100galantaminecurcumingalantamine–curcumin hybridbutyrylcholinesteraseinhibitor of butyrylcholinesterasemolecular dynamics |
| spellingShingle | Evdokiya Salamanova Mariyana Atanasova Irini Doytchinova A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study Chemistry galantamine curcumin galantamine–curcumin hybrid butyrylcholinesterase inhibitor of butyrylcholinesterase molecular dynamics |
| title | A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study |
| title_full | A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study |
| title_fullStr | A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study |
| title_full_unstemmed | A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study |
| title_short | A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study |
| title_sort | novel galantamine curcumin hybrid inhibits butyrylcholinesterase a molecular dynamics study |
| topic | galantamine curcumin galantamine–curcumin hybrid butyrylcholinesterase inhibitor of butyrylcholinesterase molecular dynamics |
| url | https://www.mdpi.com/2624-8549/6/6/100 |
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