التفاصيل البيبلوغرافية
| العنوان: |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates. |
| المؤلفون: |
Piemontese, Luca, Tomás, Daniel, Hiremathad, Asha, Capriati, Vito, Candeias, Emanuel, Cardoso, Sandra M., Chaves, Sílvia, Santos, M. Amélia |
| المصدر: |
Journal of Enzyme Inhibition & Medicinal Chemistry; Dec2018, Vol. 33 Issue 1, p1212-1224, 13p |
| مصطلحات موضوعية: |
DONEPEZIL, ALZHEIMER'S disease treatment, ACETYLCHOLINESTERASE inhibitors, DRUG development, CHELATING agents, MOIETIES (Chemistry) |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Enzyme Inhibition & Medicinal Chemistry is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder