Academic Journal
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates
| Title: | Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates |
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| Authors: | Luca Piemontese, Daniel Tomás, Asha Hiremathad, Vito Capriati, Emanuel Candeias, Sandra M. Cardoso, Sílvia Chaves, M. Amélia Santos |
| Source: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 33, Iss 1, Pp 1212-1224 (2018) |
| Publisher Information: | Taylor & Francis Group, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Therapeutics. Pharmacology |
| Subject Terms: | Alzheimer’s disease, multipotent drugs, donepezil mimetics, AChE inhibitors, anti-Aβ aggregation, Therapeutics. Pharmacology, RM1-950 |
| More Details: | A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0–30.0 μΜ) and moderate ability for inhibition of Aβ1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1475-6366 1475-6374 14756366 |
| Relation: | https://doaj.org/toc/1475-6366; https://doaj.org/toc/1475-6374 |
| DOI: | 10.1080/14756366.2018.1491564 |
| Access URL: | https://doaj.org/article/576dcbc606174caaba74b8e132d38b00 |
| Accession Number: | edsdoj.576dcbc606174caaba74b8e132d38b00 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 14756366 14756374 |
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| DOI: | 10.1080/14756366.2018.1491564 |
| Published in: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Language: | English |