Luo Yan, Wang Ke, Zhang Meng-han, Zhang Da-yong, Wu Yang-chang, Wu Xiao-ming, Hua Wei-yi
High Magnetic Field Laboratory, Chinese Academy of Sciences, Shu Shan Hu Rd No. 350, Hefei 230031, China.
Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China.
Bioorg Med Chem Lett. 2015 Jun 1;25(11):2421-4. doi: 10.1016/j.bmcl.2015.03.086. Epub 2015 Apr 4.
There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs.
关于穿心莲内酯的抗肿瘤作用修饰已有许多报道。将五元内酯环转化为呋喃芳香环仍可得到具有良好细胞毒性的化合物。为了进一步确定五元内酯环的重要性并获得更好的先导化合物，我们对穿心莲内酯中的五元内酯环进行了转化。制备了新型的对映-贝壳杉烷二萜衍生物，并对其体外细胞毒性活性进行了测定。总结了初步的构效关系，获得了两种具有良好细胞毒性活性的化合物7和26，它们有潜力被开发成新型抗肿瘤药物。
