Morphing cholinesterase inhibitor amiridine into multipotent drugs for the treatment of Alzheimer's disease
Language English Country France Media print-electronic
Document type Journal Article
PubMed
38492439
DOI
10.1016/j.biopha.2024.116399
PII: S0753-3322(24)00283-X
Knihovny.cz E-resources
- Keywords
- Acetylcholinesterase, Amiridine, Antioxidant capacity, Butyrylcholinesterase, Multi-target directed ligands, NMDA receptors,
- MeSH
- Acetylcholinesterase metabolism MeSH
- Alzheimer Disease * drug therapy metabolism MeSH
- Aminoquinolines therapeutic use MeSH
- Butyrylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors * pharmacology therapeutic use chemistry MeSH
- Humans MeSH
- Ligands MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Aminoquinolines MeSH
- amiridine MeSH Browser
- Butyrylcholinesterase MeSH
- Cholinesterase Inhibitors * MeSH
- Ligands MeSH
The search for novel drugs to address the medical needs of Alzheimer's disease (AD) is an ongoing process relying on the discovery of disease-modifying agents. Given the complexity of the disease, such an aim can be pursued by developing so-called multi-target directed ligands (MTDLs) that will impact the disease pathophysiology more comprehensively. Herewith, we contemplated the therapeutic efficacy of an amiridine drug acting as a cholinesterase inhibitor by converting it into a novel class of novel MTDLs. Applying the linking approach, we have paired amiridine as a core building block with memantine/adamantylamine, trolox, and substituted benzothiazole moieties to generate novel MTDLs endowed with additional properties like N-methyl-d-aspartate (NMDA) receptor affinity, antioxidant capacity, and anti-amyloid properties, respectively. The top-ranked amiridine-based compound 5d was also inspected by in silico to reveal the butyrylcholinesterase binding differences with its close structural analogue 5b. Our study provides insight into the discovery of novel amiridine-based drugs by broadening their target-engaged profile from cholinesterase inhibitors towards MTDLs with potential implications in AD therapy.
References provided by Crossref.org
