Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer's disease
Language English Country France Media print-electronic
Document type Journal Article
PubMed
28064079
DOI
10.1016/j.ejmech.2016.12.048
PII: S0223-5234(16)31054-6
Knihovny.cz E-resources
- Keywords
- Acetylcholinesterase, Alzheimer's disease, Amyloid, Multitarget compounds, Neuroinflammation,
- MeSH
- Acetylcholinesterase metabolism MeSH
- Alzheimer Disease drug therapy metabolism MeSH
- Amyloid beta-Peptides chemistry MeSH
- Antioxidants chemistry metabolism pharmacology therapeutic use MeSH
- Butyrylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors chemistry metabolism pharmacology therapeutic use MeSH
- Molecular Targeted Therapy * MeSH
- Blood-Brain Barrier metabolism MeSH
- Liver drug effects MeSH
- Rats MeSH
- Humans MeSH
- Ligands MeSH
- Neuroprotective Agents chemistry pharmacology therapeutic use MeSH
- Peptide Fragments chemistry MeSH
- Protein Aggregates drug effects MeSH
- Drug Design * MeSH
- Resveratrol MeSH
- Stilbenes chemistry MeSH
- Tacrine chemistry metabolism pharmacology therapeutic use MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- amyloid beta-protein (1-42) MeSH Browser
- Amyloid beta-Peptides MeSH
- Antioxidants MeSH
- Butyrylcholinesterase MeSH
- Cholinesterase Inhibitors MeSH
- Ligands MeSH
- Neuroprotective Agents MeSH
- Peptide Fragments MeSH
- Protein Aggregates MeSH
- Resveratrol MeSH
- Stilbenes MeSH
- Tacrine MeSH
Multi-target drug discovery is one of the most followed approaches in the active central nervous system (CNS) therapeutic area, especially in the search for new drugs against Alzheimer's disease (AD). This is because innovative multi-target-directed ligands (MTDLs) could more adequately address the complexity of this pathological condition. In a continuation of our efforts aimed at a new series of anti-AD MTDLs, we combined the structural features of the cholinesterase inhibitor drug tacrine with that of resveratrol, which is known for its purported antioxidant and anti-neuroinflammatory activities. The most interesting hybrid compounds (5, 8, 9 and 12) inhibited human acetylcholinesterase at micromolar concentrations and effectively modulated Aβ self-aggregation in vitro. In addition, 12 showed intriguing anti-inflammatory and immuno-modulatory properties in neuronal and glial AD cell models. Importantly, the MTDL profile is accompanied by high-predicted blood-brain barrier permeability, and low cytotoxicity on primary neurons.
References provided by Crossref.org
Anticholinesterases Traits Inbuilt in Buxaceae Plant Extracts against Alzheimer's Disease
Development of 2-Methoxyhuprine as Novel Lead for Alzheimer's Disease Therapy
