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.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- amyloidní beta-protein chemie MeSH
- antioxidancia chemie metabolismus farmakologie terapeutické užití MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemie metabolismus farmakologie terapeutické užití MeSH
- cílená molekulární terapie * MeSH
- hematoencefalická bariéra metabolismus MeSH
- játra účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- ligandy MeSH
- neuroprotektivní látky chemie farmakologie terapeutické užití MeSH
- peptidové fragmenty chemie MeSH
- proteinové agregáty účinky léků MeSH
- racionální návrh léčiv * MeSH
- stilbeny chemie MeSH
- takrin chemie metabolismus farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
