Bis selenide alkene derivatives: A class of potential antioxidant and antinociceptive agents

Bis and tris-selenide alkene derivatives, a class of organoselenium compounds, were screened for antinociceptive and antioxidant activities. In vitro, bis-selenide alkene 1c (R=2,4,6-Me3C6H2), 1d (R=4-ClC6H4) and le (R=4-MeOC6H4) protected against lipid peroxidation about 50%, whereas 1b(R=C6H5)and la (R=C4H9) protected only 23%. Compound 1d presented lesser IC50 against lipid peroxidation than other bis-selenide alkene compounds (1d > 1e >= 1c > 1a = 1b). The maximal inhibitory effect of tris-selenide alkenes on lipid peroxidation was in the following order 2c > 2a = 2b. Compound le increased the rate of GSH, but not DTT, oxidation. Tris-selenide alkene 2c (R=4-MeOC6H4) demonstrated the higher rate of thiol oxidation, while 2a (R=C6H5) did not change DTT oxidation but oxidized GSH. Conversely, compound 2b (R=4-ClC6H4) did not change the rate of GSH oxidation, but oxidized DDT. Bis-selenide alkene derivatives 1c, 1d and 1e were the most promising compounds tested in vitro. In vivo, compounds 1c and 1d (5-50mg/kg, subcutaneously) produced significant inhibition of acetic acid- and capsaicin-induced pain. Compounds 1c and 1d increased the tail-flick response latency time. The antinociception effect of 1c and 1d was not abolished by naloxone (an antagonist of opioid receptor, 1 mg/kg, subcutaneously), suggesting that the antinociceptive effect is not influenced by the opioidergic mechanism. (c) 2006 Elsevier Inc. All rights reserved.