Bifunctional agents for reperfusion arrhythmias: Novel hybrid vitamin E Class I antiarrhythmics

被引：27

作者：

Koufaki, M

Calogeropoulou, T

Rekka, E

Chryselis, M

Papazafiri, P

Gaitanaki, C

Makriyannis, A

机构：

[1] Natl Hellen Res Fdn, Inst Organ & Pharmaceut Chem, GR-11635 Athens, Greece

[2] Aristotle Univ Thessaloniki, Sch Pharm, Dept Pharmaceut Chem, Thessaloniki 54124, Greece

[3] Univ Athens, Sch Biol, Dept Anim & Human Physiol, Athens 15784, Greece

[4] Univ Connecticut, Ctr Drug Discovery, Storrs, CT 06269 USA

[5] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA

[6] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2003年 / 11卷 / 23期

关键词：

D O I：

10.1016/j.bmc.2003.08.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have synthesized a series of hybrid compounds combining the pharmacophoric redox moieties of vitamin E and key features responsible for the antiarrhythmic properties of the class I antiarrhythmics procainamide and lidocaine. Procainamide analogue (2a) and lidocaine analogues (14a) and (14b) are very strong inhibitors of lipid peroxidation. All analogues tested at 100 or 30 muM enhanced the post ischemic recovery without inducing ventricular fibrillations while there was no evidence in our experiments for drug-induced pro-arrhythmia. In addition, they induced a widening of the QRS intervals. Our data suggest that the efficacy of the new compounds in preventing reperfusion arrhythmias could be attributed to their combined effects involving inhibition of free radical mediated damage coupled with antiarrhythmic properties. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：5209 / 5219

页数：11

共 28 条

[1] IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-κB and reduces the inflammatory response in myocardial ischaemia-reperfusion injury [J].