雷公藤红素的结构修饰及抗肿瘤活性研究进展

Research Advances in Structural Modification and Antitumor Activity of Celastrol

雷公藤红素是一种来源于药用植物雷公藤(Tripterygium wilfordii Hook.f.)的五环三萜类天然活性产物,具有显著而广泛的抗肿瘤活性,然而,水溶性差、毒副作用强等缺点限制了其转化成为临床抗肿瘤药物。为此,通过结构修饰,改善其临床应用的局限性成为该研究领域的热点。迄今,针对其进行的结构修饰主要集中于A环C-2、C-3位,B环的C-6位及E环的28位,主要有酯化、酰胺化及引入药效基团等修饰,此外,部分非常见的修饰位点同样对抗肿瘤活性有重要影响。综述了近年来雷公藤红素的结构修饰及其抗肿瘤活性研究进展,为深入研究雷公藤红素的临床应用提供参考。

Celastrol,a kind of natural active product of pentacyclic triterpenes,roots in medicinal plant Tripterygium wilfordii Hook.f.It possesses significant and extensive antitumor activity.However,its conversion into clinical antitumor drugs is limited by poor water solubility,strong toxic side effects and other disadvantages.Therefore,improving its limitations of clinical applications through structural modification has attracted much attention in the research field.To date,the modification sites of celastrol mainly focused on the C-2,C-3 position of the ring-A,the C-6 position of ring-B,and the 28 position of the ring-E,including esterification,amidation,and introduction of pharmacological groups.In addition,some uncommon modification sites also have a significant impact on antitumor activity.The research progress of structural modification and antitumor activity of celatrol in recent years are reviewed,providing reference for intensive study on clinical application of it.