Sulfhydryl-Based Inhibition of δ-ALA-D and Na+ , K+ -ATPase Activities Depends on the Organoselenium Group Bonded to the Isoquinoline
| Autor: | Juliana Trevisan da Rocha, Tuane Bazanella Sampaio, Caroline B. Quines, Cristina W. Nogueira, André L. Stein, Gilson Zeni |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification biology Stereochemistry ATPase Sodium-Potassium-Exchanging ATPase Cell Biology Biochemistry Dithiothreitol 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Enzyme chemistry Dehydratase Toxicity biology.protein Na+/K+-ATPase Isoquinoline Molecular Biology 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cellular Biochemistry. 118:1144-1150 |
| ISSN: | 0730-2312 |
| Popis: | Organoselenium compounds and isoquinoline derivatives have their toxicity linked to induction of pro-oxidant situations. δ-Aminolevulinate dehydratase (δ-ALA-D) and Na+ , K+ -ATPase have sulfhydryl groups susceptible to oxidation. Thus, we investigated toxicological effects of 4-organoseleno-isoquinoline derivatives, cerebral monoamine oxidase B inhibitors, on rat cerebral δ-ALA-D and Na+ , K+ -ATPase activities and the involvement of sulfhydryl groups in vitro. Compounds substituted with fluoro (4-(4-fluorophenylseleno)-3-phenylisoquinoline), chloro (4-(4-chlorophenylseleno)-3-phenylisoquinoline) and trifluoro (4-(3-trifluoromethylphenylseleno)-3-phenylisoquinoline) at the selenium-bonded aromatic ring inhibited δ-ALA-D (IC50 values: 78.42, 92.27, 44.98 µM) and Na+ , K+ -ATPase (IC50 values: 41.36, 89.43, 50.66 µM) activities, possibly due to electronic effects induced by these groups. 3-Phenyl-4-(phenylseleno) isoquinoline (without substitution at the selenium-bonded aromatic ring) and 4-(4-methylphenylseleno)-3-phenylisoquinoline (with a methyl group substituted at the selenium-bonded aromatic ring) did not alter the activity of these enzymes. Dithiothreitol, a reducing agent, restored the enzymatic activities inhibited by 4-(4-fluorophenylseleno)-3-phenylisoquinoline, 4-(4-chlorophenylseleno)-3-phenylisoquinoline and 4-(3-trifluoromethylphenylseleno)-3-phenylisoquinoline, suggesting the involvement of sulfhydryl residues in this effect. However, the release of essential zinc seems not to be related to the δ-ALA-D inhibition by these compounds. According to these data, the effect of oral administration (300 mg/kg, intragastric) of 3-phenyl-4-(phenylseleno) isoquinoline on markers of systemic toxicity in Wistar rats was evaluated. None signs of toxicity was observed during or after treatment. This study suggests that the insertion of electron-withdrawing groups in the aromatic ring bonded to the selenium atom of isoquinolines tested increased its inhibitory effect on sulfhydryl enzymes in vitro. 3-Phenyl-4-(phenylseleno) isoquinoline, which has documented pharmacological properties, had no toxicological effects on the parameters evaluated in this study. J. Cell. Biochem. 118: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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