Efficient synthesis and cytotoxicity of novel microtubule-stabilizing agent ceratamine A analogues |
| |
Authors: | Lulu Tao Xuan Pan Ming Ji Xiaoguang Chen Zhanzhu Liu |
| |
Institution: | 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 |
| |
Abstract: | An efficient synthesis of microtubule-stabilizing agent ceratamine A analogues is described. The key step is the application of either reductive Heck reaction or Heck reaction to construct the imidazo4,5-d]azepine core. Thirteen novel analogues of ceratamine A were synthesized and evaluated for their in vitro cytotoxicity against five human cancer cell lines (HCT-116, HepG2, BGC-823, A549 and A2780). It was the first report about the systematic structural modification and SARs study of ceratamine A. The results demonstrated that bulky substituents at C-14 and C-16 could enhance the cytotoxicy and modification at N-7 was crucial for high potency. Especially compound 1f bearing methyl group at C-14 and C-16, and compound 1k bearing benzyl group on N-7, showed better cytotoxicy than ceratamine A against A549. |
| |
Keywords: | Ceratamine A Microtubule Heck reaction Anticancer |
本文献已被 ScienceDirect 等数据库收录! |
|