One Hundred Faces of Cyclopamine
One Hundred Faces of Cyclopamine
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DOI：
10.2174/1381612822666160112130157
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Botta, Bruno
中科院分区：
文献类型：
--
作者：
Iovine, Valentina;Mori, Mattia;Botta, Bruno
天然甾体生物碱环巴胺已被确定为Hedgehog（Hh）信号通路的第一个抑制剂，Hh信号通路与胚胎发育和肿瘤发生有关，并且在癌症干细胞（CSC）中过度活化。Hh依赖性肿瘤的名单正在稳步增长，据估计，所有癌症死亡中约有25%显示出异常Hh通路激活的迹象。值得注意的是，已发现环巴胺对几种类型的人类癌症发挥抗癌活性并抑制CSC增殖，从而突出了Hh途径的可药用性并为抗癌药物发现提供了新的机会。本文综述了环巴胺及其衍生物的主要合成策略，重点介绍了为提高环巴胺的生物活性而进行的化学修饰。
The natural steroidal alkaloid cyclopamine has been identified as the first inhibitor of the Hedgehog (Hh) signaling pathway, which is implicated in embryonic development and tumorigenesis, as well as is hyperactivated in cancer stem cells (CSCs). The list of Hh-dependent tumors is steadily growing, and it has been estimated that about 25% of all cancer deaths show signs of aberrant Hh pathway activation. Notably, cyclopamine has been found to exert anticancer activity against several types of human cancer and to inhibit CSCs proliferation, thus highlighting the druggability of the Hh pathway and paving new opportunities in anticancer drug discovery. The aim of the present work is to review the main synthetic strategies to cyclopamine and its derivatives, with particular emphasis on the challenging chemical modifications aimed at improving the biological activity of the molecule.