Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20817518
DOI
10.1016/j.bmcl.2010.08.044
PII: S0960-894X(10)01167-4
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase metabolism MeSH
- Alzheimer Disease drug therapy enzymology MeSH
- Butyrylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Inhibitory Concentration 50 MeSH
- Humans MeSH
- Models, Molecular MeSH
- Recombinant Proteins metabolism MeSH
- Tacrine analogs & derivatives chemical synthesis chemistry pharmacology MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 7-methoxytacrine MeSH Browser
- Acetylcholinesterase MeSH
- Butyrylcholinesterase MeSH
- Cholinesterase Inhibitors MeSH
- Recombinant Proteins MeSH
- Tacrine MeSH
All approved drugs for Alzheimer disease (AD) in clinical practice ameliorate the symptoms of the disease. Among them, acetylcholinesterase inhibitors (AChEIs) are used to increase the cholinergic activity. Among new AChEI, tacrine compounds were found to be more toxic compared to 7-MEOTA (9-amino-7-methoxy-1,2,3,4-tetrahydroacridine). In this Letter, series of 7-MEOTA analogues (N-alkyl-7-methoxytacrine) were synthesized. Their inhibitory ability was evaluated on recombinant human acetylcholinesterase (AChE) and plasmatic human butyrylcholinesterase (BChE). Three novel compounds showed promising results towards hAChE better to THA or 7-MEOTA. Three compounds resulted as potent inhibitors of hBChE. The SAR findings highlighted the C(6)-C(7)N-alkyl chains for cholinesterase inhibition.
References provided by Crossref.org
Development of 2-Methoxyhuprine as Novel Lead for Alzheimer's Disease Therapy
