Inhibition of Acetylcholinesterase by Wood Creosote and Simple Phenolic Compounds
| Autor: | Norio Ogata, Hideaki Tagishi, Motonori Tsuji |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
010402 general chemistry
01 natural sciences Anisakis law.invention chemistry.chemical_compound Structure-Activity Relationship Phenols law Drug Discovery Animals Carvacrol Thymol Essential oil Creosote chemistry.chemical_classification biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry General Chemistry General Medicine biology.organism_classification Acetylcholinesterase Wood 0104 chemical sciences Molecular Docking Simulation Enzyme chemistry Biochemistry Docking (molecular) Electrophorus Guaiacol Cholinesterase Inhibitors |
| Zdroj: | Chemicalpharmaceutical bulletin. 68(12) |
| ISSN: | 1347-5223 |
| Popis: | Anisakiasis is common in countries where raw or incompletely cooked marine fish are consumed. Currently, effective therapeutic methods to treat anisakiasis are unavailable. A recent study found that wood creosote inactivates the movement of Anisakis species. Essential oil of Origanum compactum containing carvacrol and thymol, which are similar to the constituents of wood creosote, was reported to inactivate Anisakis by inhibiting its acetylcholinesterase. We examined whether wood creosote can also inhibit acetylcholinesterase. We examined the effect of components of wood creosote using the same experimental method. A computer simulation experiment (molecular docking) was also performed. Here, we demonstrate that wood creosote inactivated acetylcholinesterase in a dose-dependent manner with an IC50 of 0.25 mg/mL. Components of wood creosote were also tested individually: 5-methylguaiacol, p-cresol, guaiacol, o-cresol, 2,4-dimethylphenol, m-cresol, phenol and 4-methylguaiacol inactivated the enzyme with an IC50 of 14.0, 5.6, 17.0, 6.3, 3.9, 10.0, 15.2 and 27.2 mM, respectively. The mechanism of acetylcholinesterase inactivation was analyzed using a computer-based molecular docking simulation, which employed a three-dimensional structure of acetylcholinesterase and above phenolic compounds as docking ligands. The simulation indicated that the phenolic compounds bind to the active site of the enzyme, thereby competitively blocking entry of the substrate acetylcholine. These findings suggest that the mechanism for the inactivation of Anisakis movement by wood creosote is due to inhibition of acetylcholinesterase needed for motor neuron activity. |
| Databáze: | OpenAIRE |
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