Department of Pharmaceutical Sciences, College of Pharmacy, Ferris State University, Big Rapids, MI, USA.
Department of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, Princess Anne, MD, USA.
Toxicol Appl Pharmacol. 2023 Jan 15;459:116362. doi: 10.1016/j.taap.2022.116362. Epub 2022 Dec 30.
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.
蒽环类抗生素是一类从土壤细菌中分离出来的天然产物，拥有超过 2000 种化学代表物。自 70 年前 Waksman 及其同事发现以来，蒽环类抗生素已成为临床应用中最具特征性的抗癌化疗药物之一。蒽环类抗生素对多种实体瘤和液体瘤具有广谱抗肿瘤活性，但其临床应用受到其剂量限制的心脏毒性的限制。在这篇综述文章中，我们讨论了蒽环类抗生素对几个器官系统的毒性，包括对多柔比星诱导的心脏毒性的新见解。此外，我们还讨论了新的药物化学发展，包括新蒽环类抗生素类似物的生物合成和心脏毒性降低的新蒽环类抗生素类似物的合成。最后，我们回顾了描述蒽环类抗生素重新定位或“升级利用”为抗感染药物或利基适应症药物的新研究。总之，由于对其心脏毒性的机制有了更深入的了解，以及对其潜在新临床应用的新发展，蒽环类抗生素仍然是临床治疗的主要药物，具有新的“生命力”。关键词：蒽环类抗生素、化疗、毒理学、药物化学、生物合成。
