摘要
为拓展马蹄金素(MTS)二肽衍生物结构多样性,以获得新型抗乙肝病毒活性目标分子,本文采用生物电子等排体替换法,将MTS二肽衍生物中容易水解的酰胺键以含有三氟甲基取代的甲氨基单元替换,设计合成了新型氟代MTS二肽模拟物。所有目标化合物均通过^(1)H NMR、^(13)C NMR、^(19)F NMR、HRMS或ESI-MS进行了结构确证,通过单晶X射线衍射测定了化合物10′的晶体结构,并以HepG22.2.15细胞模型对其进行了体外抗乙肝病毒(HBV)测试,结果显示所有目标化合物对HBV DNA的复制均有抑制作用,14e、14f、14k的IC_(50)值分别为0.37、0.29、0.79μmol·L^(-1)。
To expand the structural diversity of Matijin-Su(MTS)derivatives and explore novel anti-HBV activity compounds,a series of fluorinated dipeptidomimetics of MTS were designed and synthesized by using trifluoromethyl substituted methylamine unit as bioisostere to replace the amide bond of the MTS derivatives.The structures of all target compounds were confirmed by ^(1)H NMR,^(13)C NMR,^(19)F NMR,HRMS,or ESI-MS,and the crystal structure of 10'was determined by X-ray single crystal diffraction.Their inhibitory activity against hepatitis B virus(HBV)in vitro were evaluated using HepG22.2.15 cell model.The results showed that all target compounds had inhibitory effect on HBV DNA replication,the IC_(50) of 14e,14f,and 14k were 0.37,0.29,and 0.79μmol·L^(-1),respectively.
作者
黄维杰
况安香
邵晓霜
曾晓萍
梁光义
孟雪玲
徐必学
HUANG Wei-jie;KUANG An-xiang;SHAO Xiao-shuang;ZENG Xiao-ping;LIANG Guang-yi;MENG Xue-ling;XU Bi-xue(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences/Guizhou Provincial Engineering Research Center for Natural Drugs,Guiyang 550014,China;Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;School of Pharmacy,Guizhou Medical University,Guiyang 550025,China)
出处
《药学学报》
CAS
CSCD
北大核心
2022年第4期1095-1105,共11页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81760623)
贵州省高层次创新人才培养计划项目(黔科合平台人才[2016] 5678)。