| Autor: |
Puguh Novi Arsito, Pornthip Waiwut, Chavi Yenjai, Supakorn Arthan, Orawan Monthakantirat, Natsajee Nualkaew, Pitchayakarn Takomthong, Chantana Boonyarat |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Heliyon, Vol 9, Iss 11, Pp e21894- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2405-8440 |
| DOI: |
10.1016/j.heliyon.2023.e21894 |
| Popis: |
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuronal death. Fifteen flavonoids from Millettia brandisiana were evaluated for the multifunctional effect against AD pathogenesis, including butyrylcholine esterase (BuChE) inhibition, anti-amyloid beta (Aβ) aggregation and neuroprotection against hydrogen peroxide (H2O2) toxicity in differentiated human neuroblastoma SH-SY5Y cell. To understand the mechanism and structure-activity relationship, binding interactions between flavonoids and the BuChE and Aβ were investigated in silico. Furthermore, drug-likeness properties and ADMET parameters were evaluated in silico using SwissADME and pKCSM tools. All flavonoids exhibit a good drug-likeness profile. Six flavonoids have potency in BuChE inhibition, and four flavonoids show potency in anti-Aβ aggregation. Flavonoids with the 6″,6″-dimethylchromeno- [2″,3”:7,8]-flavone structure show a favorable multifunctional effect. In silico analysis showed that flavonoids can bind in various positions to the catalytic triad, anionic site, and acyl pocket. In Aβ1-42, potential flavonoids can attach to the central hydrophobic region and the C terminal hydrophobic and interfere with Aβ interchain hydrogen binding. When compared together, it can inhibit multifunctional action with a favorable ADMET parameter and drug-likeness profile. In addition, candidine can prevent neuronal damage in differentiated SH-SY5Y neuroblastoma cells induced by H2O2 in a dose-dependent manner. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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