Sökning: id:"swepub:oai:gup.ub.gu.se/327270" >
In silico and in vi...
In silico and in vitro studies confirm Ondansetron as a novel acetylcholinesterase and butyrylcholinesterase inhibitor
-
- Gholami, Asma (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
-
Minai-Tehrani, D. (författare)
-
- Eriksson, Leif A, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
-
(creator_code:org_t)
- 2023-01-12
- 2023
- Engelska.
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1
- Relaterad länk:
-
https://gup.ub.gu.se...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is growing rapidly among the elderly population around the world. Studies show that a lack of acetylcholine and butyrylcholine due to the overexpression of enzymes Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) may lead to reduced communication between neuron cells. As a result, seeking novel inhibitors targeting these enzymes might be vital for the future treatment of AD. Ondansetron is used to prevent nausea and vomiting caused by chemotherapy or radiation treatments and is herein shown to be a potent inhibitor of cholinesterase. Comparison is made between Ondansetron and FDA-approved cholinesterase inhibitors Rivastigmine and Tacrine. Molecular docking demonstrates that interactions between the studied ligand and aromatic residues in the peripheral region of the active site are important in binding. Molecular dynamics simulations and binding pose metadynamics show that Ondansetron is highly potent against both enzymes and far better than Rivastigmine. Inhibitor activities evaluated by in vitro studies confirm that the drug inhibits AChE and BChE by non-competitive and mixed inhibition, respectively, with IC50 values 33 mu M (AChE) and 2.5 mu M (BChE). Based on the findings, we propose that Ondansetron may have therapeutic applications in inhibiting cholinesterase, especially for BChE.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- activity spectra
- prediction
- cimetidine
- mechanism
- catalase
- binding
- protein
- Science & Technology - Other Topics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas