Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties.
A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents.
Department of Pharmacodynamic, Laboratory of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. jaceksapa@interia.pl
Jacek
J
Sapa
Alicja
A
Nowaczyk
Katarzyna
K
Kulig
D018674:Adrenergic Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D017609:Barium Compounds / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D005117:Cardiac Complexes, Premature / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D002712:Chlorides / Q000494:pharmacology; D015195:Drug Design; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D015428:Myocardial Reperfusion Injury / Q000150:complications; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control
D018674:Adrenergic Antagonists; D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D017609:Barium Compounds; D002712:Chlorides; D011760:Pyrrolidinones; C024986:barium chloride