Pan Xuan, Tao Lulu, Ji Ming, Chen Xiaoguang, Liu Zhanzhu
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
Bioorg Med Chem Lett. 2018 Mar 1;28(5):866-868. doi: 10.1016/j.bmcl.2018.02.004. Epub 2018 Feb 9.
A series of novel imidazo[4,5-d]azepine compounds derived from marine natural product ceratamine A were designed and synthesized in 7 steps. Most compounds exhibited comparable cytotoxicity against five human cancer cell lines (HCT-116, HepG2, BGC-823, A549 and A2780) to natural product ceratamine A. Compound 1k, bearing methoxy group at C-14, C-15 and C-16, showed the best in vitro cytotoxicity, which was better than ceratamine A. The structure and activity relationships study showed that the benzyloxymethyl group on N-3 played an important role on the cytotoxicity.
通过7步反应设计并合成了一系列源自海洋天然产物角胺A的新型咪唑并[4,5-d]氮杂卓化合物。大多数化合物对五种人类癌细胞系（HCT-116、HepG2、BGC-823、A549和A2780）表现出与天然产物角胺A相当的细胞毒性。在C-14、C-15和C-16位带有甲氧基的化合物1k表现出最佳的体外细胞毒性，优于角胺A。构效关系研究表明，N-3位的苄氧基甲基对细胞毒性起重要作用。
