Novel potent inhibitors of lipid peroxidation with protective effects against reperfusion arrhythmias

M Koufaki; T Calogeropoulou; A Detsi; A Roditis; A P Kourounakis; P Papazafiri; K Tsiakitzis; C Gaitanaki; I Beis; P N Kourounakis

doi:10.1021/jm010962w

Novel potent inhibitors of lipid peroxidation with protective effects against reperfusion arrhythmias

J Med Chem. 2001 Nov 22;44(24):4300-3. doi: 10.1021/jm010962w.

Authors

M Koufaki¹, T Calogeropoulou, A Detsi, A Roditis, A P Kourounakis, P Papazafiri, K Tsiakitzis, C Gaitanaki, I Beis, P N Kourounakis

Affiliation

¹ Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vasileos Constantinou Avenue, 11635 Athens, Greece. [email protected]

PMID: 11708933
DOI: 10.1021/jm010962w

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Arrhythmia Agents / chemical synthesis*
Anti-Arrhythmia Agents / chemistry
Anti-Arrhythmia Agents / pharmacology
Antioxidants / chemical synthesis*
Antioxidants / chemistry
Antioxidants / pharmacology
Arrhythmias, Cardiac / etiology
Arrhythmias, Cardiac / prevention & control*
Benzopyrans / chemical synthesis*
Benzopyrans / chemistry
Benzopyrans / pharmacology
Chromans / chemical synthesis*
Chromans / chemistry
Chromans / pharmacology
Depression, Chemical
Diamines / chemical synthesis
Diamines / chemistry
Diamines / pharmacology
In Vitro Techniques
Lipid Peroxidation / drug effects*
Microsomes, Liver / drug effects
Microsomes, Liver / metabolism
Myocardial Reperfusion Injury / complications
Myocardial Reperfusion Injury / prevention & control*
Rats
Structure-Activity Relationship
Thioctic Acid / analogs & derivatives*
Thioctic Acid / chemical synthesis*
Thioctic Acid / chemistry
Thioctic Acid / pharmacology

Substances

Anti-Arrhythmia Agents
Antioxidants
Benzopyrans
Chromans
Diamines
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
N-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)ethylenediamine
Thioctic Acid
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid