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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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Chemistry |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2624-8549/6/6/100 |
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| Summary: | 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. |
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| ISSN: | 2624-8549 |