Preparation, in vitro screening and molecular modelling of symmetrical 4-tert-butylpyridinium cholinesterase inhibitors--analogues of SAD-128
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21144749
DOI
10.1016/j.bmcl.2010.11.051
PII: S0960-894X(10)01663-X
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase chemistry metabolism MeSH
- Cholinesterase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Catalytic Domain MeSH
- Models, Molecular MeSH
- Organophosphates chemistry MeSH
- Computer Simulation MeSH
- Pyridinium Compounds chemical synthesis chemistry pharmacology MeSH
- Binding Sites MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Cholinesterase Inhibitors MeSH
- Organophosphates MeSH
- Pyridinium Compounds MeSH
- SAD-128 MeSH Browser
Carbamate inhibitors (e.g., pyridostimine bromide) are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. They work by blocking acetylcholinesterase's (AChE) native function and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, carbamate inhibitors are known for many undesirable side-effects related to the carbamylation of AChE. In this Letter, 19 analogues of SAD-128 were prepared and evaluated as cholinesterase inhibitors. The screening results showed promising inhibitory ability of four compounds better to used standards (pralidoxime, obidoxime, BW284c51, ethopropazine, SAD-128). Four most promising compounds were selected for further molecular docking studies. The SAR was stated from obtained data. The former receptor studies were reported and discussed. The further in vivo studies were recommended in the view of OP pre-exposure treatment.
References provided by Crossref.org
Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study
