中文摘要：

天然产物倍半萜内酯如青蒿素等具有重要的药用价值,Dehydrozaluzanin C是一种从兔耳风等药用植物根部提取分离的愈创木内酯类倍半萜内酯,为解决其生物含量的问题、了解其抗肿瘤活性,本研究设计出一种快速、高效的合成方法获得Dehydrozaluzanin C,探讨该化合物对膀胱癌T24细胞增殖、细胞凋亡的影响.实验结果表明,以去氢木香内酯为起始反应物,通过烯丙位氧化、戴斯-马丁氧化两步反应从而获得Dehydrozaluzanin C,总产率为73%.细胞增殖MTT实验结果表明该化合物能显著地制膀胱癌T24细胞的增殖,且该抑制作用呈现出明显的剂量依赖效应;DAPI染色结果表明该化合物能显著诱导T24细胞凋亡,Western Blot免疫印迹分析结果证实该化合物在分子水平上通过PARP的断裂从而诱导细胞凋亡.上述结果表明愈创木内酯Dehydrozaluzanin C对膀胱癌的预防与治疗具有潜在价值.

英文摘要：

Sesquiterpenoid lactones such as artemisinin from natural products have an important pharmaceutical potential. Dehydrozaluzanin C, a kind of guaianolide sesquiterpenoid lactone, is originally isolated from medicinal plants like A insliaea DC. However, the extremely low content in those plants limits its further development and utilization. So far the anti-cancer activity of Dehydrozaluzanin C remains largely unknown. In this study, Dehydrozaluzanin C was synthesized by a rapid and efficient method, and the anti-proliferative and apoptotic effects on human bladder cancer T24 cells were further investigated. Firstly, Dehydrozaluzanin C was synthesized beginning with dehydrocostuslactone in two steps including allylic and Dess- Martin oxidation, and the total yield was 73%. Furthermore, MTT assays showed that Dehydrozaluzanin C significantly inhibited the proliferation of bladder cancer T24 cells in a dose-dependent manner. Moreover, DAPI staining demonstrated that Dehydrozaluzanin C significantly induced the apoptosis of bladder cancer T24 cells. Mechanistically, western blot analysis further confirmed that the apoptotic effect of Dehydrozaluzanin C was associated with activation of the cleavage of PARP, leading to the apoptotic effect ofT24 cells. Taken together, these findings suggest that guaianolide Dehydrozaluzanin C may be a promising lead compound for prevention and treatment of bladder cancer.