التفاصيل البيبلوغرافية
| العنوان: |
Rivastigmine–Benzimidazole Hybrids as Promising Multitarget Metal-Modulating Compounds for Potential Treatment of Neurodegenerative Diseases |
| المؤلفون: |
David Vicente-Zurdo, Leonardo Brunetti, Luca Piemontese, Beatriz Guedes, Sandra M. Cardoso, Daniel Chavarria, Fernanda Borges, Yolanda Madrid, Sílvia Chaves, M. Amélia Santos |
| المصدر: |
International Journal of Molecular Sciences; Volume 24; Issue 9; Pages: 8312 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
Alzheimer’s disease, Parkinson’s disease, rivastigmine hybrids, metal chelation, cholinesterases, monoamine oxidase, amyloid-β aggregation |
| جغرافية الموضوع: |
agris |
| الوصف: |
With the goal of combating the multi-faceted Alzheimer’s disease (AD), a series of Rivastigmine-Benzimidazole (RIV–BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-β (Aβ) aggregation. Herein, we moved forward in this project, studying their ability to chelate redox-active biometal ions, Cu(II) and Fe(III), with widely recognized roles in the generation of oxidative reactive species and in protein misfolding and aggregation in both AD and Parkinson’s disease (PD). Although Cu(II) chelation showed higher efficiency for the positional isomers of series 5 than those of series 4 of the hybrids, the Aβ-aggregation inhibition appears more dependent on their capacity for fibril intercalation than on copper chelation. Since monoamine oxidases (MAOs) are also important targets for the treatment of AD and PD, the capacity of these hybrids to inhibit MAO-A and MAO-B was evaluated, and they showed higher activity and selectivity for MAO-A. The rationalization of the experimental evaluations (metal chelation and MAO inhibition) was supported by computational molecular modeling studies. Finally, some compounds showed also neuroprotective effects in human neuroblastoma (SH-SY5Y cells) upon treatment with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxic metabolite of a Parkinsonian-inducing agent. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Molecular Pharmacology; https://dx.doi.org/10.3390/ijms24098312Test |
| DOI: |
10.3390/ijms24098312 |
| الإتاحة: |
https://doi.org/10.3390/ijms24098312Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.2DE3E77F |
| قاعدة البيانات: |
BASE |
