Synthesis, pharmacological study and docking calculations of new benzo[f]coumarin derivatives as dual inhibitors of enzymatic systems involved in neurodegenerative diseases
| Autor: | Nicholas P. Tatonetti, Rosa María González Franco, Eugenio Uriarte, Dolores Viña, Fernanda Borges, Maria João Matos, José Angel Fontenla, Santiago Vilar, Patricia Janeiro, Lourdes Santana |
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| Rok vydání: | 2014 |
| Předmět: |
Gene isoform
Monoamine Oxidase Inhibitors Aché Stereochemistry Structure-Activity Relationship chemistry.chemical_compound Coumarins Catalytic Domain Drug Discovery Humans Monoamine Oxidase IC50 Pharmacology chemistry.chemical_classification Binding Sites Neurodegenerative Diseases Coumarin language.human_language In vitro Molecular Docking Simulation Neuroprotective Agents Enzyme chemistry Docking (molecular) Butyrylcholinesterase Acetylcholinesterase language Molecular Medicine Cholinesterase Inhibitors Selectivity Protein Binding |
| Zdroj: | Future Medicinal Chemistry. 6:371-383 |
| ISSN: | 1756-8927 1756-8919 |
| Popis: | Background: Due to the complex etiology of neurodegenerative diseases, there is growing interest in multitarget drugs. In this study we synthesized and evaluated a new series of compounds, with benzo[f]coumarin structure, as potential inhibitors of MAO-A, MAO-B, AChE and BuChE. Results: In vitro studies show that most of the studied compounds inhibited the activity of MAO-B in the nano- to micro-molar range. 3-(3´-methoxyphenyl)benzo[f]coumarin is the most active compound with an IC50 value against MAO-B of 2.44 nM. Most of the derivatives exhibited an important selectivity profile against the MAO-B isoform. Some of them also acted as in vitro inhibitors of BuChE, with 3-(2´-hydroxyphenyl)benzo[f]coumarin being the most active with an IC50 value of 1.13 µM. In addition, a theoretical study of the physicochemical properties of the new compounds, as well as a docking study in both MAO isoforms, were carried out. Important structure–activity relationships were obtained. Conclusion: Important preliminary structure–activity relationships were concluded from the experimental results. These results encourage us to further explore the potential of this chemical family as potential drug candidates for the treatment of Alzheimer‘s disease. |
| Databáze: | OpenAIRE |
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