喜树碱
化学
拓扑替康
前药
伊立替康
拓扑异构酶
序号38
结构-活动关系
计算生物学
立体化学
药理学
组合化学
生物化学
酶
体外
癌症
生物
遗传学
结直肠癌
化疗
作者
Xianzhang Wang,Yumeng Zhuang,Yuankun Wang,Maokai Jiang,Lei Yao
标识
DOI:10.1016/j.ejmech.2023.115710
摘要
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.
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