Click-chemistry Synthesis and Antitumor Properties of Cyclometalated Iridium(iii) Complex Based on Oleanolic Acid

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-N-3 to obtain the final complex CycloIr-OA via copper(I)-catalyzed azide. alkyne cycloaddition (CuAAC) reaction. The ligand and the complex were characterized by H-1 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.