Departamento de Química, Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Mol Cell Biochem. 2009 Dec;332(1-2):17-24. doi: 10.1007/s11010-009-0169-3. Epub 2009 Jun 9.
Toxicological and pharmacological studies demonstrated that the introduction of functional groups into the aromatic ring of diphenyl diselenide alter its effect. The aim of this study was to evaluate the in vitro effect of m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities in rat brain homogenates. Diselenides inhibited delta-ALA-D activity (IC(50) 4-6 microM [concentration inhibiting 50%]), and dithiothreitol (DTT) restored the enzyme activity. ZnCl(2) (100 microM) did not restore delta-ALA-D inhibition caused by (p-Cl-C(6)H(4)Se)(2) and (m-CF(3)-C(6)H(4)Se)(2). Na(+), K(+)-ATPase activity was more sensitive to (p-Cl-C(6)H(4)Se)(2) and (m-CF(3)-C(6)H(4)Se)(2) (IC(50) 6 microM) than (p-CH(3)O-C(6)H(4)Se)(2) and (PhSe)(2) (IC(50) 45 and 31 microM, respectively). DTT restored the activity of Na(+), K(+)-ATPase inhibited by diselenides. The effect of diselenides on Na(+)/K(+)-ATPase is dependent on their substitutions in the aromatic ring. The mechanism through which diselenides inhibit delta-ALA-D and Na(+), K(+)-ATPase activities involves the oxidation of thiol groups.
毒理学和药理学研究表明，将功能基团引入二苯二硒醚的芳环中会改变其作用。本研究旨在评估间三氟甲基-二苯二硒醚（m-CF(3)-C(6)H(4)Se)(2)、对氯-二苯二硒醚（p-Cl-C(6)H(4)Se)(2)和对甲氧基-二苯二硒醚（p-CH(3)O-C(6)H(4)Se)(2)对大鼠脑匀浆中δ-氨基酮戊酸脱水酶（δ-ALA-D）和 Na(+), K(+)-ATPase 活性的体外影响。二硒醚抑制 δ-ALA-D 活性（IC(50) 4-6 microM [抑制 50%的浓度]），二硫苏糖醇（DTT）可恢复酶活性。100 μM 的 ZnCl(2)不能恢复 (p-Cl-C(6)H(4)Se)(2)和 (m-CF(3)-C(6)H(4)Se)(2)引起的 δ-ALA-D 抑制。Na(+), K(+)-ATPase 活性对 (p-Cl-C(6)H(4)Se)(2)和 (m-CF(3)-C(6)H(4)Se)(2)（IC(50) 6 microM）比对 (p-CH(3)O-C(6)H(4)Se)(2)和 (PhSe)(2)（IC(50) 分别为 45 和 31 microM）更敏感。DTT 可恢复二硒醚抑制的 Na(+), K(+)-ATPase 活性。二硒醚对 Na(+)/K(+)-ATPase 的作用取决于其在芳环上的取代基。二硒醚抑制 δ-ALA-D 和 Na(+), K(+)-ATPase 活性的机制涉及巯基的氧化。
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