Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2603844 | Toxicology in Vitro | 2007 | 5 Pages |
Abstract
Organochalcogens are important intermediates and useful reagents in organic synthesis. Recent data from our laboratory demonstrated that bis and tris-selenide alkene derivatives are attractive synthetic targets because of their chemio-, regio- and stereo-selective reactions. Since the erythrocytic δ-aminolevulinate dehydratase (δ-ALA-D) activity could be an important indicator of toxicity, this report investigated bis and tris-selenide alkene derivatives effects on blood δ-ALA-D in vitro. To investigate the mechanisms by which these compounds inhibit human blood δ-ALA-D activity, a thiol reducing agent or zinc chloride were used. 1,2-Bis-selenide alkene derivatives 1a (R = 4-MeOC6H4), 1b (R = 4-ClC6H4) and 1c (R = 2,4,6-Me3C6H2) did not inhibit human blood δ-ALA-D activity. 1,1,2-Tris-selenide alkene derivative 2a (R = C6H5) was the most potent δ-ALA-D inhibitor. Compounds 2b (R = 4-MeOC6H4) and 2c (R = 4-ClC6H4) displayed similar inhibitory potency towards δ-ALA-D activity. Dithiothreitol, a hydrophobic SH-reducing agent, was able to restore and to protect δ-ALA-D activity inhibited by tris-selenide alkene derivatives. Conversely, ZnCl2 did not alter the enzyme inhibition induced by tris-selenide alkene derivatives. From these findings we suggest that 1,1,2-tris-selenide alkene derivatives inhibited δ-ALA-D activity by an interaction with essential sulfhydryl groups for the enzyme activity.
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Authors
Vanessa C. Borges, Gabriele Dadalt, Lucielli Savegnago, Angélica V. Moro, Joao B.T. Rocha, Cristina W. Nogueira,