التفاصيل البيبلوغرافية
| العنوان: |
Novel Rivastigmine Derivatives as Promising Multi-Target Compounds for Potential Treatment of Alzheimer’s Disease |
| المؤلفون: |
David Vicente-Zurdo, Noelia Rosales-Conrado, M. Eugenia León-González, Leonardo Brunetti, Luca Piemontese, A. Raquel Pereira-Santos, Sandra M. Cardoso, Yolanda Madrid, Sílvia Chaves, M. Amélia Santos |
| المصدر: |
Biomedicines; Volume 10; Issue 7; Pages: 1510 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2022 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
Alzheimer’s disease, multi-target drugs, rivastigmine, neurodegenerative, amyloid aggregation, acetylcholinesterase, butyrylcholinesterase |
| الوصف: |
Alzheimer’s disease (AD) is the most serious and prevalent neurodegenerative disorder still without cure. Since its aetiology is diverse, recent research on anti-AD drugs has been focused on multi-target compounds. In this work, seven novel hybrids (RIV–BIM) conjugating the active moiety of the drug rivastigmine (RIV) with 2 isomeric hydroxyphenylbenzimidazole (BIM) units were developed and studied. While RIV assures the inhibition of cholinesterases, BIM provides further appropriate properties, such as inhibition of amyloid β-peptide (Aβ) aggregation, antioxidation and metal chelation. The evaluated biological properties of these hybrids included antioxidant activity; inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and Aβ42 aggregation; as well as promotion of cell viability and neuroprotection. All the compounds are better inhibitors of AChE than rivastigmine (IC50 = 32.1 µM), but compounds of series 5 are better inhibitors of BChE (IC50 = 0.9−1.7 µM) than those of series 4. Series 5 also showed good capacity to inhibit self- (42.1−58.7%) and Cu(II)-induced (40.3−60.8%) Aβ aggregation and also to narrow (22.4−42.6%) amyloid fibrils, the relevant compounds being 5b and 5d. Some of these compounds can also prevent the toxicity induced in SH-SY5Y cells by Aβ42 and oxidative stress. Therefore, RIV–BIM hybrids seem to be potential drug candidates for AD with multi-target abilities. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Neurobiology and Neurologic Disease; https://dx.doi.org/10.3390/biomedicines10071510Test |
| DOI: |
10.3390/biomedicines10071510 |
| الإتاحة: |
https://doi.org/10.3390/biomedicines10071510Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.35182BE8 |
| قاعدة البيانات: |
BASE |
