Evaluation of cardiotoxicity of a new antitumor compound, anthrafuran, a derivative of anthracycline antibiotics

Abstract

Introduction: Anthracyclines and anthracenedione derivatives are a group of anticancer drugs that are widely used in clinical practice. Their application is frequently limited by cardiotoxic effects. The aim of this study was to evaluate the cardiotoxicity of the new anthracenedione derivative Anthrafuran (AF) in comparison with Doxorubicin (Dox) and Mitoxantrone (MT).

Materials and Methods: The study was conducted on 50 adult female Wistar rats. AF, MT, and Dox were administered in therapeutic doses and regimens for this animal species (AF: 20 mg/kg x 3/48 per os; MT: 1 mg/kg x 3/96 i.v.; Dox: 2.5 mg/kg x 3/72 i.v.). Electrocardiographic (ECG) parameters and heart weight index were determined; histological evaluation of the myocardium was performed on days 1 and 30 post-treatment.

Results: Dox intravenous injections in therapeutic doses caused a pronounced cardiotoxic effect. The signs of cardiac decompensation manifested as a significant decrease in heart rate (HR) (Dox 486±6, control 522±12.8), prolongation of the QT interval (Dox 0.06±0.002, control 0.048±0.001), an increase in weight index of the heart (Dox 0.41±0.03, control 0.36±0.006), and myocardial damage. Although the cardiotoxicity of MT was less pronounced, it nevertheless negatively affected both ECG parameters (HR 465±15, QT 0.056±0.002) and the structure of the heart muscle. The use of AF did not cause any pathological changes and had no effect on the heart weight index or ECG parameters (HR 498±7.3, QT 0.052±0.003, weight index of the heart 0.35±0.009).

Conclusion: Unlike Dox (2.5 mg/kg x 3/72 i.v.) and MT (1 mg/kg x 3/96 i.v.), the new anthracenedione derivative AF (20 mg/kg x 3/48 per os) in therapeutic doses does not possess cardiotoxic properties, supporting its potential for clinical study.

Graphical Abstract