Disubstituted diaryl diselenides inhibit delta-ALA-D and Na+, K+-ATPase activities in rat brain homogenates in vitro.
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.
Brüning
César Augusto
CA
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.
Prigol
Marina
M
Barancelli
Daniela A
DA
Nogueira
Cristina Wayne
CW
Zeni
Gilson
G
D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology*; D002712:Chlorides / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017967:Zinc Compounds / Q000494:pharmacology
D001555:Benzene Derivatives; D002712:Chlorides; D004791:Enzyme Inhibitors; D016566:Organoselenium Compounds; D017967:Zinc Compounds; C061132:diphenyldiselenide; C016837:zinc chloride; D000623:Porphobilinogen Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D004229:Dithiothreitol