Sixteen tropinone derivatives were prepared,and their antitumor activities against five human cancer cells(HL-60,A-549,SMMC-7721,MCF-7 and SW480)were evaluated with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methox...Sixteen tropinone derivatives were prepared,and their antitumor activities against five human cancer cells(HL-60,A-549,SMMC-7721,MCF-7 and SW480)were evaluated with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium]assay.Most of the derivatives exhibited better activities compared with tropinone at the concentration of 40 pM.Particularly,derivative 6 showed significant activities with IC50 values of 3.39,13.59,6.65,13.09 and 12.38 pM respectively against HL-60,A-549,SMMC-7721,MCF-7 and SW480 cells,which suggested more potent activities than that of cis-dichlorodiamineplatinum(DDP).展开更多
洋金花的入药成分是莨菪碱和东莨菪碱,托品酮还原酶Ⅰ(tropinone reductase I, TRI)是托品烷类生物碱合成途径中的关键酶,该酶的编码基因是TAs代谢工程研究重要的靶标基因。本研究从洋金花中克隆TRⅠ基因,命名为Dm TRⅠ(GenBank登录号:M...洋金花的入药成分是莨菪碱和东莨菪碱,托品酮还原酶Ⅰ(tropinone reductase I, TRI)是托品烷类生物碱合成途径中的关键酶,该酶的编码基因是TAs代谢工程研究重要的靶标基因。本研究从洋金花中克隆TRⅠ基因,命名为Dm TRⅠ(GenBank登录号:MW455085)。DmTRⅠ基因包含一个822 bp的完整开放阅读框,编码273个氨基酸。生物信息学分析发现,DmTRⅠ为稳定的亲水性蛋白,是DmTRⅠ作为辅酶NADPH的结合位点,有TGXXXGXG保守结构域。从生物进化关系上发现,DmTRⅠ与同为茄科的颠茄、三分三等5种植物的TRⅠ聚为一支,且与曼陀罗属的木本曼陀罗TRI亲缘关系最近。进一步以ACTIN和PGK双基因为内参基因,DmTRⅠ基因表达分析显示,DmTRⅠ在根、茎、叶、花、果实各器官中均有表达,其中根的表达量最高,花,茎、叶的表达量较低,在果实中表达量最低。DmTRⅠ基因的获得及表达分析为进一步研究洋金花TAs的生物合成提供理论依据。展开更多
基金supported by the Hundred Talents Program of the Chinese Academy of Sciences(CAS),the Youth Innovation Promotion Association,CAS and the Program of Yunling Scholarship.
文摘Sixteen tropinone derivatives were prepared,and their antitumor activities against five human cancer cells(HL-60,A-549,SMMC-7721,MCF-7 and SW480)were evaluated with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium]assay.Most of the derivatives exhibited better activities compared with tropinone at the concentration of 40 pM.Particularly,derivative 6 showed significant activities with IC50 values of 3.39,13.59,6.65,13.09 and 12.38 pM respectively against HL-60,A-549,SMMC-7721,MCF-7 and SW480 cells,which suggested more potent activities than that of cis-dichlorodiamineplatinum(DDP).
