| Autor: |
Bosak, Anita, Matošević, Ana, Primožič, Ines, Opsenica, Dejan, Komatović, Katarina, Zandona, Antonio, Bartolić, Marija |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Popis: |
The primary goal of the project is to develop molecules with the potential to alleviate the symptoms and slow down the progression of neurodegenerative diseases that primarily affect the neurons in the human brain that causes problems with movement and/or mental functioning. As the best results in restoration of cognitive functions of patients and alleviating the symptoms of the disease are done using drugs that targets cholinesterases (ChE), the project aims to rationally design dual site binding ChE inhibitors (acting on improving the acetylcholine level in the brain and on Aβ aggregation) and use them as starting points for multitarget-directed ligand (MTDL) design. We focused our study on butyrylcholinesterase (BChE) selective inhibitors due to the role of the BChE in the regulation of brain ACh levels in late AD and the fact that selective inhibition of BChE reduces the occurrence of side effects seen with the acetylcholinesterase (AChE) or nonselective ChE inhibitors currently in use. In design of potential bioactive molecules, we chosen two structural scaffolds, each with different mode of action with ChE’s. A carbamate functionality was chosen due to the similarity of mechanism of their interaction with choliesterases with the mechanism of AChE hydrolysis of its physiological substrate ACh. Aminoquinoline, as a structural motive, gained our attention due to their similarity to tacrine, the first centrally acting cholinesterase inhibitor approved for the treatment of Alzheimer’s disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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