Bibliographic Details
| Title: |
Novel Rivastigmine Derivatives as Promising Multi-Target Compounds for Potential Treatment of Alzheimer’s Disease |
| Authors: |
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 |
| Source: |
Biomedicines, Vol 10, Iss 7, p 1510 (2022) |
| Publisher Information: |
MDPI AG, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Alzheimer’s disease, multi-target drugs, rivastigmine, neurodegenerative, amyloid aggregation, acetylcholinesterase, Biology (General), QH301-705.5 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2227-9059 |
| Relation: |
https://www.mdpi.com/2227-9059/10/7/1510; https://doaj.org/toc/2227-9059 |
| DOI: |
10.3390/biomedicines10071510 |
| Access URL: |
https://doaj.org/article/bb8b37ac68d846fe80f3c1a79f47530c |
| Accession Number: |
edsdoj.bb8b37ac68d846fe80f3c1a79f47530c |
| Database: |
Directory of Open Access Journals |
