Journal Article

Low Molecular Weight Modifications of Anthracycline Antibiotics. Part I. Reactions by Amino Group (A Review)

Semakov, A. V

2024

Overview

Abstract—Anthracyclines are a class of antibiotics of natural origin with anthraquinone chromophore and their synthetic analogs. Since their clinical introduction 50 years ago, anthracyclines have remained a cornerstone of antitumor drug therapy. Over the decades, substantial research has been conducted on the chemical modification of anthracyclines, elucidation of structure–activity relationships for each atom within the molecule, and the de novo synthesis of synthetic analogs featuring non-natural aglycones or sugars. This review highlights the chemical reactions of anthracyclines, with a particular focus on daunorubicin and doxorubicin, which have been most extensively studied as substrates. The primary pathways for chemical modification of these molecules are detailed, including reactions at the amino group (yielding acyl, alkyl, or urethane derivatives), the carbonyl group of the aglycone, and esterification at the alcohol group of the aglycone. Less commonly explored modifications at other positions in the aglycone and amino sugar are also discussed. Many of these modifications result in altered biological activity, influencing both antitumor efficacy and the cardiotoxicity commonly associated with anthracyclines.

• Publisher: Springer Nature B.V
• Subject: Aglycones / Analogs / Anthracycline / Anthraquinone / Anthraquinones / Antibiotics / Anticancer properties / Antitumor activity / Biological activity / Biological effects / Carbonyl groups / Carbonyls / Cardiotoxicity / Cell cycle / Chemical modification / Chemical reactions / Chemical synthesis / Chemistry / Chemotherapy / Chromophores / Clinical significance / Cytotoxicity / Daunorubicin / Doxorubicin / Drug therapy / Enzymes / Esterification / Low molecular weights / Metabolites / Microorganisms / Molecular weight / Sugar / Toxicity