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-Me(3)C(6)H(2)), 1d (R=4-ClC(6)H(4)) and 1e (R=4-MeOC(6)H(4)) protected against lipid peroxidation about 50%, whereas 1b (R=C(6)H(5)) and 1a (R=C(4)H(9)) protected only 23%. Compound 1d presented lesser IC(50) against lipid peroxidation than other bis-selenide alkene compounds (1d>1e> or =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-MeOC(6)H(4)) demonstrated the higher rate of thiol oxidation, while 2a (R=C(6)H(5)) did not change DTT oxidation but oxidized GSH. Conversely, compound 2b (R=4-ClC(6)H(4)) 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, 1mg/kg, subcutaneously), suggesting that the antinociceptive effect is not influenced by the opioidergic mechanism.
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Lucielli
L
Savegnago
Cristiano R
CR
Jesse
Angélica V
AV
Moro
Vanessa C
VC
Borges
Francielli W
FW
Santos
Joao B T
JB
Rocha
Cristina W
CW
Nogueira
D000475:Alkenes / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002211:Capsaicin / Q000008:administration & dosage; D004229:Dithiothreitol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009292:Narcotic Antagonists; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism; D010146:Pain / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000737:chemistry*
D000475:Alkenes; D000700:Analgesics; D000975:Antioxidants; D009292:Narcotic Antagonists; D050862:Oxidoreductases Acting on Sulfur Group Donors; C112161:thiol oxidase, 47 kDa; D005978:Glutathione; D012643:Selenium; D002211:Capsaicin; D004229:Dithiothreitol