Synthesis and activity of miconazole derivatives as dual BChE/IDO1 inhibitors for the treatment of Alzheimer's disease
| Autor: | Feng Feng, Wenyuan Liu, Haopeng Sun, Yao Chen, Xin Lu, Hongyu Yang, Yijun Liu, Nan Qin, Yuting Qiao, You Zhou, Xueyang Jiang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Models Molecular Kynurenine pathway Miconazole Morris water navigation task Disease Neurological disorder Pharmacology PC12 Cells 03 medical and health sciences Mice Protein Aggregates 0302 clinical medicine Alzheimer Disease Cell Line Tumor Drug Discovery medicine Animals Humans Horses 030304 developmental biology Cholinesterase 0303 health sciences Amyloid beta-Peptides biology Behavior Animal business.industry medicine.disease Peptide Fragments Rats Neuroprotective Agents Cell culture Butyrylcholinesterase Electrophorus biology.protein Molecular Medicine Cholinergic Cholinesterase Inhibitors business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Future medicinal chemistry. 13(13) |
| ISSN: | 1756-8927 |
| Popis: | Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease. |
| Databáze: | OpenAIRE |
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