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 1e (R = 4-MeOC6H4) protected against lipid peroxidation about 50%, whereas 1b (R = C6H5) and 1a (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 1e 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 (5–50 mg/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.