4-Organoseleno-Isoquinolines Selectively and Reversibly Inhibit the Cerebral Monoamine Oxidase B Activity
| Autor: | Juliana Trevisan da Rocha, Marina Prigol, João Rocha, Gilson Zeni, Rogério de Aquino Saraiva, Cristina W. Nogueira, Pablo Froner Nogara, André L. Stein, Tuane Bazanella Sampaio |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Monoamine Oxidase Inhibitors Monoamine oxidase Stereochemistry Quantitative Structure-Activity Relationship chemistry.chemical_element Mixed inhibition 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Organoselenium Compounds medicine Animals Rats Wistar Isoquinoline Monoamine Oxidase IC50 Trifluoromethyl Selegiline Brain General Medicine Isoquinolines Mitochondria Rats Molecular Docking Simulation 030104 developmental biology chemistry Biochemistry Monoamine oxidase B 030217 neurology & neurosurgery Selenium Protein Binding medicine.drug |
| Zdroj: | Journal of Molecular Neuroscience. 59:135-145 |
| ISSN: | 1559-1166 0895-8696 |
| Popis: | Isoquinolines are formed endogenously as metabolites of neurotransmitters and are studied because they have structures similar to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and selegiline, a selective inhibitor of MAO-B. This study investigated a possible in vitro inhibitory activity of new 4-organochalcogen-isoquinoline derivatives, containing sulfur 1, selenium 2 or tellurium 3 on MAO-A and B activities. Considering that the non-substituted selenoisoquinoline derivative 2 showed the best inhibitory profile (IC50 = 36.45 μM), new compounds were synthesized by adding substituents (methyl 2a, fluorine 2b, chloro 2c and trifluoromethyl 2d) to the aromatic ring bonded to the selenium atom of compound 2. All tested compounds were selective MAO-B inhibitors, although only the substituted isoquinoline derivative 2b showed IC50 lower than the concentration of 100 μM (IC50 = 82.41 μM). Compounds 2 and 2b were chosen to study the inhibitory profile. These compounds demonstrated reversible and mixed inhibition by decreasing apparent V (app) max and increasing apparent K (app) m, however the non-substituted compound 2 was a more potent inhibitor than the substituted compound 2b (K i = 7.07 and 16.30 μM). In conclusion, selenoisoquinolines 2 and 2b fit in the profile of third generation MAO inhibitors (selective and reversible), which are promising alternatives for treatment of emotional and neurodegenerative disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink