Zhang Jun, Liu Ling-Li, Zhong Ba-Lian, Liao Xiao-Jian, Xu Shi-Hai
College of Pharmacy, Jinan University, Guangzhou 510632, PR China; National Engineering Research Centre of Navel Orange, Gannan Normal University, Ganzhou 341000, PR China.
Division of Life Science, School of Science, The Hong Kong University of Science and Technology, Hong Kong Special Administrative Region.
Steroids. 2015 Jun;98:100-6. doi: 10.1016/j.steroids.2015.03.004. Epub 2015 Mar 18.
Nine new 9,11-secosterols (1-9), containing the same 3β,6α,11-trihydroxy-9,11-seco-5α-cholest-7-en-9-one steroidal nucleus, whereas possessing an array of structurally diverse side chains, along with fourteen known 9,11-secosterol compounds (10-23), were isolated from the South China Sea gorgonian coral Subergorgia suberosa, of which 3/4, 5/6, 7/8, and the known compounds 11/12, 20/21 were five pairs of inseparable C-24 epimers. Their structures were established by the extensive analyses of 1D and 2D NMR spectra, high-resolution chemical ionization mass spectrometry (HRCIMS), and by the comparison with literature data. Cytotoxic effect of these metabolites against the growth of HeLa cell lines was evaluated. The result showed that the inhibitory effect of compounds 1-23 varied considerably depending on the nature of the side chain in spite of sharing the same steroidal nucleus. Compound 19, featuring both the absence of hydroxyl group and the presence of double bond in the stigmasterol side chain, exhibited the most potent cytotoxicity with IC50 being 15.1 μM. The preliminary structure activity relationship studies identified some important structural features considerably influencing the biological effect deserved, providing valuable information for chemists and pharmacologists to design and synthesize more effective antitumor agents bearing the 9,11-secosteroid framework.
从中国南海柳珊瑚亚侧柳珊瑚（Subergorgia suberosa）中分离得到了9个新的9,11-断甾醇（1-9），它们具有相同的3β,6α,11-三羟基-9,11-断-5α-胆甾-7-烯-9-酮甾体核，但其侧链结构多样，同时还分离得到了14个已知的9,11-断甾醇化合物（10-23），其中3/4、5/6、7/8以及已知化合物11/12、20/21是五对不可分离的C-24差向异构体。通过对一维和二维核磁共振谱、高分辨化学电离质谱（HRCIMS）的广泛分析以及与文献数据的比较确定了它们的结构。评估了这些代谢产物对HeLa细胞系生长的细胞毒性作用。结果表明，尽管化合物1-23共享相同的甾体核，但它们的抑制作用因侧链性质的不同而有很大差异。化合物19在豆甾醇侧链上既没有羟基又有双键，表现出最强的细胞毒性，IC50为15.1 μM。初步的构效关系研究确定了一些对生物学效应有显著影响的重要结构特征，为化学家和药理学家设计和合成更有效的具有9,11-断甾体骨架的抗肿瘤药物提供了有价值的信息。
