Synthesis, molecular docking and molecular dynamics studies of novel tacrine-carbamate derivatives as potent cholinesterase inhibitors
| Autor: | Fatih Sonmez, Ozge Ozten, Belma Zengin Kurt, Serdar Durdagi, Berna Dogan |
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| Přispěvatelé: | ZENGİN KURT, BELMA |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Carbamate Molecular model Stereochemistry Ozten O. ZENGİN KURT B. Sonmez F. Dogan B. Durdagi S. -Synthesis molecular docking and molecular dynamics studies of novel tacrine-carbamate derivatives as potent cholinesterase inhibitors- Bioorganic Chemistry cilt.115 2021 medicine.medical_treatment Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Humans Molecular Biology Butyrylcholinesterase Cholinesterase chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure biology Organic Chemistry Acetylcholinesterase Enzyme chemistry Docking (molecular) Tacrine biology.protein Carbamates Cholinesterase Inhibitors medicine.drug |
| Zdroj: | Bioorganic Chemistry. 115:105225 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2021.105225 |
| Popis: | © 2021 Elsevier Inc.In the present study, new tacrine derivatives containing carbamate group were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities were evaluated. All synthesized compounds inhibited both cholinesterases at nanomolar level. Among them, ((1,2,3,4-tetrahydroacridin-9-yl)amino)ethyl(3-nitrophenyl) carbamate (6k) showed the best inhibitor activity against AChE and BuChE with IC50 value of 22.15 nM and 16.96 nM, respectively. The calculated selectivity index revealed that the synthesized compounds (exclude 6l) have stronger inhibitory activity against BuChE than AChE. The most selective compound was 2-((1,2,3,4-tetrahydroacridin-9-yl)amino)ethyl(4-methoxyphenyl)-carbamate (6b) with the selectivity index of 0.12. Molecular modeling approaches were employed to understand the interaction between the synthesized compounds and proteins. As carbamate derivatives can act as pseudo-irreversible inhibitors of AChE and BuChE, covalent docking approaches was applied to determine the binding modes of novel compounds at binding sites of cholinesterase enzymes. |
| Databáze: | OpenAIRE |
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