Novel potent inhibitors of lipid peroxidation with protective effects against reperfusion arrhythmias.
A series of new compounds that contain lipoic acid and trolox connected through spacers were synthesized and examined for their antioxidant activity and their protective effects against reperfusion arrhythmias in isolated heart preparations. All compounds tested are strong inhibitors of lipid peroxidation in rat liver microsomal membranes induced by ferrous ions and ascorbate. N-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)-1,2-phenylenediamine (13) exhibits anti-lipid peroxidation activity at the nanomolar range. N-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)ethylenediamine (10) and 13 totally suppressed reperfusion arrhythmias.
Koufaki
M
M
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vasileos Constantinou Avenue, 11635 Athens, Greece. mkoufa@eie.gr
Calogeropoulou
T
T
Detsi
A
A
Roditis
A
A
Kourounakis
A P
AP
Papazafiri
P
P
Tsiakitzis
K
K
Gaitanaki
C
C
Beis
I
I
Kourounakis
P N
PN
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003864:Depression, Chemical; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D051381:Rats; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D001578:Benzopyrans; D002839:Chromans; D003959:Diamines; C440624:N-(3,4-dihydro-6-hydroxy--2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)-1,2-phenylenediamine; C440623:N-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)ethylenediamine; D008063:Thioctic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid