7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24929293
DOI
10.1016/j.ejmech.2014.05.066
PII: S0223-5234(14)00490-5
Knihovny.cz E-resources
- Keywords
- 7-MEOTA, AChE/BChE inhibitors, Alzheimer's disease, Molecular modeling, QSAR, Tacrine,
- MeSH
- Acetylcholinesterase metabolism MeSH
- Butyrylcholinesterase blood metabolism MeSH
- Cholinesterase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Donepezil MeSH
- Electrophorus MeSH
- Indans chemistry pharmacology MeSH
- Horses MeSH
- Quantitative Structure-Activity Relationship * MeSH
- Humans MeSH
- Models, Molecular MeSH
- Molecular Structure MeSH
- Piperidines chemistry pharmacology MeSH
- Recombinant Proteins metabolism MeSH
- Tacrine analogs & derivatives chemistry pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals 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
- Donepezil MeSH
- Indans MeSH
- Piperidines MeSH
- Recombinant Proteins MeSH
- Tacrine MeSH
A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like derivatives can be considered as interesting candidates for Alzheimer's disease treatment.
References provided by Crossref.org
Substituted Piperazines as Novel Potential Radioprotective Agents
In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
Development of 2-Methoxyhuprine as Novel Lead for Alzheimer's Disease Therapy
