RESUMO
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 delta-aminolevulinate dehydratase (delta-ALA-D) activity could be an important indicator of toxicity, this report investigated bis and tris-selenide alkene derivatives effects on blood delta-ALA-D in vitro. To investigate the mechanisms by which these compounds inhibit human blood delta-ALA-D activity, a thiol reducing agent or zinc chloride were used. 1,2-Bis-selenide alkene derivatives 1a (R=4-MeOC(6)H(4)), 1b (R=4-ClC(6)H(4)) and 1c (R=2,4,6-Me(3)C(6)H(2)) did not inhibit human blood delta-ALA-D activity. 1,1,2-Tris-selenide alkene derivative 2a (R=C(6)H(5)) was the most potent delta-ALA-D inhibitor. Compounds 2b (R=4-MeOC(6)H(4)) and 2c (R=4-ClC(6)H(4)) displayed similar inhibitory potency towards delta-ALA-D activity. Dithiothreitol, a hydrophobic SH-reducing agent, was able to restore and to protect delta-ALA-D activity inhibited by tris-selenide alkene derivatives. Conversely, ZnCl(2) 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 delta-ALA-D activity by an interaction with essential sulfhydryl groups for the enzyme activity.
