Multiple drug resistance

Chemistry

Toxicity

Chemotherapy

Drug

Biochemistry

Glycoside

Topoisomerase

Cancer

Antibiotics

Anthracycline

Aglycone

Daunorubicin

Breast cancer

Internal medicine

Cardiotoxicity

Topoisomerase inhibitor

Stereochemistry

Pharmacology

In vitro

Medicine

ChemMedChem

Anthracyclines are ranked among the most effective chemotherapeutics against cancer. They are glycoside drugs comprising the amino sugar daunosamine linked to a hydroxy anthraquinone aglycone, and act by DNA intercalation, oxidative stress generation and topoisomerase II poisoning. Regardless of their therapeutic value, multidrug resistance and severe cardiotoxicity are important limitations of anthracycline treatment that have prompted the discovery of novel analogues. This review covers the most clinically relevant anthracyclines and their development over decades, since the first discovered natural prototypes to recent semisynthetic and synthetic derivatives. These include registered drugs, drug candidates undergoing clinical trials, and compounds under pre‐clinical investigation. The impact of the structural modifications on antitumour activity, toxicity and resistance profile is addressed.

Antitumour Anthracyclines: Progress and Perspectives