Bu Ming, Cao Tingting, Li Hongxia, Guo Mingzhou, Yang Burton B, Zhou Yue, Zhang Na, Zeng Chengchu, Hu Liming
Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
Chinese PLA General Hospital, Beijing 100853, China.
Steroids. 2017 Aug;124:46-53. doi: 10.1016/j.steroids.2017.05.013. Epub 2017 Jun 9.
By inspiration of significant anti-cancer activity of our previously screened natural ergosterol peroxide (EP), a series of novel steroidal 5α,8α-endoperoxide derivatives 5a-d and 14a-f were designed, synthesized, and biologically evaluated for their in vitro anti-proliferative inhibitory and cytotoxic activity. The results revealed that most of these compounds showed moderate-to-excellent anti-proliferative effects against the tested cancer cell lines (i.e. HepG2, SK-Hep1, MDA-MB-231 and MCF-7). Among them, compound 5b and 14d exhibited preferable inhibitory activities (IC of 5b and 14d are 8.07 and 9.50μM against HepG2, respectively). The structure-activity relationships indicated that incorporation the peroxidic bridge to the steroid scaffolds at C-5 and C-8 positions together with the aliphatic side-chain at the C-17 position would provide synergistic effect for the bioactivity.
鉴于我们之前筛选出的天然过氧化麦角甾醇（EP）具有显著的抗癌活性，设计、合成了一系列新型甾体5α,8α-内过氧化物衍生物5a-d和14a-f，并对其体外抗增殖抑制和细胞毒性活性进行了生物学评价。结果表明，这些化合物中的大多数对测试的癌细胞系（即HepG2、SK-Hep1、MDA-MB-231和MCF-7）表现出中度至优异的抗增殖作用。其中，化合物5b和14d表现出较好的抑制活性（5b和14d对HepG2的IC分别为8.07和9.50μM）。构效关系表明，在C-5和C-8位将过氧桥引入甾体骨架并结合C-17位的脂肪族侧链将为生物活性提供协同效应。
