1,1,2-Tris-organoselenide alkene derivatives, but not 1,2-bis-organoselenide alkene derivatives, inhibited δ-aminolevulinate dehydratase activity from human erythrocytic cells in vitro

Organochalcogens are important intermediates and useful reagents in organic synthesis. Recent data from our laboratory demonstrated that his 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 his 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 la (R = 4-MeOC6H4), 1b (R = 4-ClC6H4) and 1c (R = 2,4,6-Me3C6H2) (lid not inhibit human blood delta-ALA-D activity. 1, 1,2-Tris-selenide alkene derivative 2a (R = C6H5) was the most potent delta-ALA-D inhibitor. Compounds 2b (R = 4-MeOC6H4) and 2c (R = 4-ClC6H4) 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, 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 delta-ALA-D activity by an interaction with essential sulfhydryl groups for the enzyme activity. (c) 2006 Elsevier Ltd. All rights reserved.