Antioxidant activity of novel indole derivatives and protection of the myocardial damage in rabbits.
Novel indole derivatives containing a triazole moiety (1a-d, 2a-c) were synthesized as lead compounds with interesting pharmacological profiles. Their antioxidant activity was investigated on in vitro non-enzymatic rat hepatic microsomal lipid peroxidation. All compounds showed significant effect in the above assay. The effect depended mainly on the attachment position of the triazole moiety on the indole nucleus. The most potent antioxidant derivatives la, 1c and 1d were tested for their protective ability against the oxidative damage of the myocardium after ischemia-reperfusion, in male rabbits which were subjected to 30 min regional ischemia followed by reperfusion. The tested antioxidant compounds 1a, 1c and 1d were continuously infused for 30 min starting at 10th min of ischemia and lasted at 10th min of reperfusion. The concentration of malondialdehyde (MDA, a marker of lipid peroxidation) and hemodynamic parameters (blood pressure and heart rate) were measured in the baseline, at 20th min of the sustained ischemia, 1st and 20th min of reperfusion. It was found that the examined compounds la, 1c and 1d reduced significantly the level of MDA in rabbits under ischemia-reperfusion and proved to be promising substances for further evaluation of anti-ischemic properties.
Andreadou
Ioanna
I
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Greece.
Tasouli
Androniki
A
Bofilis
Elias
E
Chrysselis
Michael
M
Rekka
Eleni
E
Tsantili-Kakoulidou
Anna
A
Iliodromitis
Efstathios
E
Siatra
Theodora
T
Kremastinos
Dimitrios Thoma
DT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D007211:Indoles; D020011:Protective Agents; D008315:Malondialdehyde