Antioxidant properties of new chalcogenides against lipid peroxidation in rat brain.
Ebselen (2-phenyl- 1,2-benzisoselenazole-3 (2H)-one) is a seleno-organic compound with antioxidant properties, and anti-inflammatory actions. Recently, ebselen improved the outcome of acute ischemic stroke in humans. In the present study, the potential antioxidant capacity of organochalcogenide compounds diphenyl diselenide (PhSe)2, diphenyl ditelluride (PhTe)2, diphenyl disulfide (PhS)2, p-Cl-diphenyl diselenide (pCl-PhSe)2, bis-[S-4-isopropyl 2-phenyl oxazoline] diselenide (AA-Se)2, bis-[S-4-isopropyl 2-phenyl oxazoline] ditelluride (AA-Te)2 and bis-[S-4-isopropyl 2-phenyl oxazoline] disulfide (AA-S)2 was compared with that of ebselen (a classical antioxidant). Spontaneous and quinolinic acid (QA)- (2 mM) and sodium nitroprusside (SNP)- (5 microM)-induced thiobarbituric reactive species (TBARS) production by rat brain homogenates was determined colorimetrically. TBARS formation was reduced by ebselen, (PhSe)2, (PhTe)2, (AA-Se)2, (AA-S)2 and (pCl- PhSe)2 to basal rates. The concentrations of these compounds needed to inhibit TBARS formation by 50% (IC50) are 1.71 microM, 3.73 microM, 1.63 microM, 9.85 microM, >33.3 microM, 23.2 microM and 4.83 microM, respectively for QA. For TBARS production induced by SNP the IC50 was 2.02 microM, 12.5 microM, 2.80 microM, >33.3 microM, 24.5 microM and 7.55 microM, respectively. The compounds (AA-Te)2 and (PhS)2 have no antioxidant activity and pro-oxidant activity, respectively. These results suggest that (AA-Se)2 and (AA-S)2 can be considered as potential pharmaceutical antioxidant agents.
Rossato
J I
JI
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brasil.
Ketzer
L A
LA
Centurião
F B
FB
Silva
S J N
SJ
Lüdtke
D S
DS
Zeni
G
G
Braga
A L
AL
Rubin
M A
MA
Rocha
J B T
JB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018011:Chalcogens / Q000494:pharmacology*; D004220:Disulfides / Q000494:pharmacology; D054833:Isoindoles; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D016566:Organoselenium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001393:Azoles; D001555:Benzene Derivatives; D018011:Chalcogens; D004220:Disulfides; D054833:Isoindoles; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; C042986:ebselen; C053871:diphenyl disulfide