The long story of camptothecin: From traditional medicine to drugs
The long story of camptothecin: From traditional medicine to drugs
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DOI：
10.1016/j.bmcl.2016.12.085
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发表时间：
2017-02-15
影响因子：
2.7
通讯作者：
Collina, Simona
中科院分区：
文献类型：
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作者：
Martino, Emanuela;Della Volpe, Serena;Collina, Simona
20-(S)-喜树碱（CPT）是从喜树（中国快乐树）的树皮中提取的天然生物碱。它是一种具有抗肿瘤活性的DNA拓扑异构酶1毒药，但其使用受到稳定性和溶解度低以及不可预测的药物-药物相互作用的限制。自20世纪后期以来，它已广泛用于癌症治疗，由于从植物组织中提取的产量非常低，各种合成路线已被开发出来以满足对CPT的需求增长。此外，SAR研究允许开发更有效的CPT类似物拓扑替康和伊立替康。不幸的是，耐药性已经在几个肿瘤系中出现。需要进一步的研究来更好地了解取代基与耐药之间的关系，其临床相关性以及相关基因多态性的影响。最新的研究方法之一集中在修改递送模式，以提高肿瘤细胞的摄取和降低毒性。(C) 2016 Elsevier Ltd.版权所有。
20-(S)-Camptothecin (CPT) is a natural alkaloid extracted from the bark of Camptotheca acuminata (Chinese happy tree). It acts as a DNA topoisomerase 1 poison with an interesting antitumor activity and its use is limited by low stability and solubility and unpredictable drug-drug interactions. Since the late 20th century, it has been widely used in cancer therapy and, since extraction yields from plant tissues are very low, various synthetic routes have been developed to satisfy the increase in demand for CPT. Moreover, SAR studies have allowed for the development of more potent CPT analogues topotecan and irinotecan. Unfortunately, resistance has already occurred in several tumour lines. Additional studies are needed to better understand the relationship between substituents and resistance, its clinical relevance and the impact of related gene polymorphism. One of the latest research approaches focuses on modifying the delivery mode to improve tumour cell uptake and reduce toxicity. (C) 2016 Elsevier Ltd. All rights reserved.