齐墩果酸-环金属铱配合物的点击化学合成及抗肿瘤性能  

Click-chemistry synthesis and antitumor properties of cyclometalated iridium(Ⅲ)complex based on oleanolic acid

作　　者：李世杰 钱晓婷 黄元镭 薛旭玲 钱勇[1] 苏志 刘红科[1] LI Shi-Jie;QIAN Xiao-Ting;HUANG Yuan-Lei;XUE Xu-Ling;QIAN Yong;SU Zhi;LIU Hong-Ke(School of Chemistry and Materials Science,Nanjing Normal University,Nanjing 210023,China)

机构地区：[1]南京师范大学材料与科学学院,南京210023

出　　处：《无机化学学报》2023年第2期317-326,共10页Chinese Journal of Inorganic Chemistry

基　　金：国家自然科学基金(No.21771109,22077066,21807060)资助。

摘　　要：选择天然产物齐墩果酸进行炔基化修饰(OA-alkyne),与环金属铱前体CycloIr-N3在铜催化条件下发生叠氮-炔环加成(CuAAC)反应,得到新的环金属铱配合物CycloIr-OA,通过1H NMR、ESI-MS对配体及配合物进行了表征。配合物具有良好的脂溶性,可以快速进入细胞。用MTT法、激光共聚焦成像及流式细胞术对CycloIr-OA的抗肿瘤活性和抗癌机制进行了研究。结果表明,连接齐墩果酸后,配合物CycloIr-OA的抗癌活性有较大提升。CycloIr-OA富集在肿瘤细胞的线粒体中,导致活性氧产生,同时将细胞周期阻滞在S期,最终诱导肿瘤细胞坏死。Herein,we modified the natural product oleanolic acid with alkyne to synthesize the ligand OA-alkyne,and tethered it with cyclic metal iridium precursor CycloIr-N3to obtain the final complex CycloIr-OA via copper(Ⅰ)-catalyzed azide-alkyne cycloaddition(CuAAC)reaction.The ligand and the complex were characterized by~1H NMR and ESI-MS.The results show that the complex had good lipophilicity,which was helpful to enter the cells quickly.The antitumor activity of CycloIr-OA and the mechanism of inducing tumor cell death were further studied by MTT,confocal imaging,and flow cytometry.After oleanolic acid was linked,the anti-cancer activity of complex CycloIr-OA was greatly improved.CycloIr-OA is enriched in the mitochondria of tumor cells,leading to the production of reactive oxygen species,and at the same time,it blocks the cell cycle in the S phase,ultimately inducing tumor cell necrosis.

关 键 词：环金属铱配合物 齐墩果酸 抗肿瘤 坏死 

分 类 号：O614.821[理学—无机化学]