This review article focuses on the research progress made in the structural modifications of camptothecin (CPT), a potent cytotoxic natural alkaloid. CPT possesses a unique 5-fused ring structure and exhibits various beneficial activities such as anti-proliferative, anti-fungal, insecticidal, and anti-SARS-CoV-2 properties. CPT and its analogs, including Topotecan and Irinotecan, have been successfully developed and marketed as topoisomerase I inhibitors. To enhance the therapeutic potential of CPT, researchers have undertaken structural modifications primarily on the A, B, and E rings of the CPT core structure. These modifications aim to improve the efficacy, selectivity, and pharmacokinetic properties of CPT derivatives. The article reviews the advancements in hybridizing CPT with other bioactive compounds, the synthesis of novel CPT analogs, and their associated biological activities. Moreover, the structure-activity relationship (SAR) of these modified CPT derivatives is summarized to gain insights into their structure-function correlations. In addition to discussing the modifications and biological activities of CPT derivatives, the article also touches upon the mechanism of parent drug release. Many CPT derivatives are prodrugs, meaning they require metabolic activation to generate the active form of the drug. It is a resource for researchers interested in developing novel anti-tumor agents based on CPT, addressing the limitations associated with the parent drug, and exploring various aspects of CPT modifications.

本文重点介绍了一种强效细胞毒性天然生物碱喜树碱（CPT）的结构修饰研究进展。CPT 具有独特的 5 稠环结构，具有多种有益活性，例如抗增殖、抗真菌、杀虫和抗 SARS-CoV-2 特性。CPT 及其类似物，包括拓扑替康和伊立替康，已作为拓扑异构酶 I 抑制剂成功开发并上市。为了增强 CPT 的治疗潜力，研究人员主要对 CPT 核心结构的 A、B 和 E 环进行了结构修饰。这些修饰旨在提高喜树碱衍生物的功效、选择性和药代动力学特性。本文综述了喜树碱与其他生物活性化合物杂交、新型喜树碱类似物的合成及其相关生物活性的进展。此外，还总结了这些修饰的喜树碱衍生物的结构-活性关系（SAR），以深入了解它们的结构-功能相关性。除了讨论喜树碱衍生物的修饰和生物活性外，本文还涉及母体药物的释放机制。许多喜树碱衍生物是前药，这意味着它们需要代谢活化才能产生药物的活性形式。它为有兴趣开发基于 CPT 的新型抗肿瘤药物、解决与母体药物相关的局限性以及探索 CPT 修饰的各个方面的研究人员提供了资源。