Chimie médicale

Anthracycline In Medicinal Chemistry: Chemistry, SARs, Mechanism Of Cardiotoxicity And Preventive Strategies

Abstract

Narmin Hamaamin Hussen*, Gashbeen Osman Muhammed, Akar Yousif Yassin, Parwa Ahmed Esmail and Roza Rafiq Salih

Anthracyclines are among the most effective anticancer drugs ever developed. Cardiotoxicity is a well-known anthracycline side effect that restricts the total amount of medication given and can result in heart failure in some patients. Anthracyclines are thought to cause cardiotoxicity after one electron reduction with ROS overproduction or two electron reduction with conversion to C-13 alcohol metabolites, according to the pathophysiology of anthracycline induced cardiotoxicity. Overproduction of Reactive Oxygen Species (ROS) is likely to be the cause of anthracycline induced acute cardiotoxicity, but not all aspects of progressive cardiomyopathy. Secondary alcohol metabolites can play an important role in promoting cardiotoxicity's progression to end stage cardiomyopathy and congestive heart failure.

This review will provide an overview of the molecular mechanisms responsible for anthracycline induced cardiotoxicity focusing on the pathogenic role of Reactive Oxygen Species (ROS) and/or anthracycline secondary alcohol metabolites; and, lastly, on the most promising strategies to minimize or prevent anthracycline induced cardiotoxicity.