Synthesis, characterization and in vitro evaluation of substituted N-(2-phenylcyclopropyl)carbamates as acetyl- and butyrylcholinesterase inhibitors
| Autor: | Břetislav Brož, Radim Havelek, Katarína Vorčáková, Miloš Sedlák, Pavel Drabina, Šárka Štěpánková, Karel Královec, Eva Horáková |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Carbamate Stereochemistry Cell Survival medicine.medical_treatment 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Jurkat Cells Structure-Activity Relationship Drug Discovery medicine Humans Cytotoxicity IC50 Butyrylcholinesterase Cholinesterase Pharmacology biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry General Medicine Acetylcholinesterase In vitro 0104 chemical sciences 030104 developmental biology chemistry Lipophilicity biology.protein Carbamates Cholinesterase Inhibitors |
| Zdroj: | Journal of enzyme inhibition and medicinal chemistry. 31(sup3) |
| ISSN: | 1475-6374 |
| Popis: | A serie of O-substituted N-2-phenylcyclopropylcarbamates was prepared and characterized. These carbamates were tested as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was found, that these compounds exhibit moderate inhibition activity with values of IC50 in the range of 54.8–94.4 μM (for AChE) and up to 5.8 μM (for BChE). The AChE/BChE selectivity for each carbamate was calculated. These values varied from 0.50 to 9.46, two carbamate derivatives inhibited only AChE selectively. The most promising derivative was prepared in all optically pure forms (four isomers). It was found that individual stereoisomers differed only slightly in the inhibition ability. The cytotoxicity of all carbamates was evaluated using the standard in vitro test with Jurkat cells. With regard to their inhibition activity and cytotoxicity as well as easy preparation, O-substituted N-2-phenylcyclopropylcarbamates can be considered as promising compounds for potential medicinal applications. |
| Databáze: | OpenAIRE |
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