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Review
. 2023 Jan 15:459:116362.
doi: 10.1016/j.taap.2022.116362. Epub 2022 Dec 30.

Upcycling the anthracyclines: New mechanisms of action, toxicology, and pharmacology

Claudine E Bayles  1 , Danielle E Hale  1 , Ali Konieczny  1 , Veronica D Anderson  1 , Claire R Richardson  1 , Katelyn V Brown  1 , Jennifer T Nguyen  1 , Jacob Hecht  1 , Nora Schwartz  1 , Madan K Kharel  2 , Felix Amissah  1 , Thomas C Dowling  1 , S Eric Nybo  3
Affiliations
Review

Upcycling the anthracyclines: New mechanisms of action, toxicology, and pharmacology

Claudine E Bayles et al. Toxicol Appl Pharmacol. .

Abstract

The anthracyclines are a family of natural products isolated from soil bacteria with over 2000 chemical representatives. Since their discovery seventy years ago by Waksman and co-workers, anthracyclines have become one of the best-characterized anticancer chemotherapies in clinical use. The anthracyclines exhibit broad-spectrum antineoplastic activity for the treatment of a variety of solid and liquid tumors, however, their clinical use is limited by their dose-limiting cardiotoxicity. In this review article, we discuss the toxicity of the anthracyclines on several organ systems, including new insights into doxorubicin-induced cardiotoxicity. In addition, we discuss new medicinal chemistry developments in the biosynthesis of new anthracycline analogs and the synthesis of new anthracycline analogs with diminished cardiotoxicity. Lastly, we review new studies that describe the repurposing of the anthracyclines, or "upcycling" of the anthracyclines, as anti-infective agents, or drugs for niche indications. Altogether, the anthracyclines remain a mainstay in the clinic with a potential new "lease on life" due to deeper insight into the mechanism underlying their cardiotoxicity and new developments into potential new clinical indications for their use. Keywords: Anthracycline, chemotherapy, toxicology, medicinal chemistry, biosynthesis.

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Conflict of interest statement

Declaration of Competing Interest Stephen Eric Nybo reports financial support was provided by National Science Foundation. Stephen Eric Nybo reports financial support was provided by National Institutes of Health.

Figures

Figure 1
Figure 1
Organ toxicities caused by systemic administration of doxorubicin.
Figure 2
Figure 2
Structures of anthracyclines discussed in this manuscript.
See this image and copyright information in PMC

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