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Novel Donepezil–Arylsulfonamide Hybrids as Multitarget-Directed Ligands for Potential Treatment of Alzheimer's Disease
| Content Provider | MDPI |
|---|---|
| Author | Sonia, Calò Jo, ão Magalhães Queda, Fausto Gwizdala, Karolina Cardoso, Sandra Chaves, Sílvia Piemontese, Luca Santos, M. |
| Copyright Year | 2021 |
| Description | Alzheimer’s disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD therapies. Herein, a series of hybrid compounds are reported which were designed and developed by combining an aryl-sulfonamide function with a benzyl-piperidine moiety, the pharmacophore of donepezil (a current anti-AD acetylcholinesterase AChE inhibitor drug) or its benzyl-piperazine analogue. The in vitro results indicate that some of these hybrids achieve optimized activity towards two main AD targets, by displaying excellent AChE inhibitory potencies, as well as the capability to prevent amyloid-β (Aβ) aggregation. Some of these hybrids also prevented Aβ-induced cell toxicity. Significantly, drug-like properties were predicted, including for blood-brain permeability. Compound 9 emerged as a promising multi-target lead compound (AChE inhibition (IC50 1.6 μM); Aβ aggregation inhibition 60.7%). Overall, this family of hybrids is worthy of further exploration, due to the wide biological activity of sulfonamides. |
| Starting Page | 1658 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules26061658 |
| Journal | Molecules |
| Issue Number | 6 |
| Volume Number | 26 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-03-16 |
| Access Restriction | Open |
| Subject Keyword | Molecules Medicinal Chemistry Arylsulfonamide Donepezil Anti-neurodegeneratives Alzheimer´s Disease Ache Inhibitors Aβ Aggregation |
| Content Type | Text |
| Resource Type | Article |
