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Sulfhydryl‐Based Inhibition of δ‐ALA‐D and Na + , K + ‐ATPase Activities Depends on the Organoselenium Group Bonded to the Isoquinoline
Author(s) -
Sampaio Tuane Bazanella,
da Rocha Juliana Trevisan,
Quines Caroline Brandão,
Stein André Luiz Agnes,
Zeni Gilson,
Nogueira Cristina Wayne
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25740
Subject(s) - isoquinoline , chemistry , atpase , group (periodic table) , stereochemistry , enzyme , biochemistry , organic chemistry
ABSTRACT 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 (IC 50 values: 78.42, 92.27, 44.98 µM) and Na + , K + ‐ATPase (IC 50 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.