School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Stanford Cancer Institute, Member of Academic Council, Stanford University, USA.
J Inorg Biochem. 2018 Sep;186:42-50. doi: 10.1016/j.jinorgbio.2018.05.005. Epub 2018 May 23.
Two types of α-N-heterocyclic piperidylthiosemicarbazone ligands and related Ga(III) complexes were synthesized. The structure of Ga4 and Ga5 were characterized by X-ray single crystal diffraction. We generated the related α-N-heterocycliperidinylthiosemicarbazone analogs to examine the effect of aldehydes or ketones in the Schiff base. The antitumor activity of both type ligands increased after coordination with gallium. Interestingly, the antitumor activity of gallium complexes containing pyridyl groups (first type ligands) is higher than that of pyrazine group-containing (second type ligands) complexes. Gallium complexes significantly depleted cellular iron, resulting in upregulation of transferrin receptor-1 and downregulation of ferritin. They also effectively activate the caspase family proteins (caspase-3/7/9), promote the release of cytochromes from the mitochondria, and ultimately lead to apoptosis.
两种类型的α-N-杂环哌啶硫代缩氨基脲配体及其相关 Ga(III)配合物被合成。Ga4 和 Ga5 的结构通过 X 射线单晶衍射进行了表征。我们生成了相关的α-N-杂环哌啶基硫代缩氨基脲类似物，以研究醛或酮在席夫碱中的影响。与镓配位后，两种类型配体的抗肿瘤活性均增加。有趣的是，含吡啶基（第一类配体）的镓配合物的抗肿瘤活性高于含吡嗪基（第二类配体）的配合物。镓配合物可显著消耗细胞内铁，导致转铁蛋白受体-1 上调和铁蛋白下调。它们还能有效激活半胱天冬酶家族蛋白（caspase-3/7/9），促进细胞色素从线粒体释放，最终导致细胞凋亡。
