Design Synthesis and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells

摘要

Three iridium(III) complexes ([Ir(Hppy)2(L)](PF6) (Hppy = 2-phenylpyridine, L = 5-nitrophenanthroline, NP), >1; 5-nitro-6-amino-phenanthroline (NAP), >2; and 5,6-diamino-phenanthroline (DAP) >3 were synthesized and characterized. The cytotoxicities of Ir(III) complexes >1–>3 against cancer cell lines SGC-7901, A549, HeLa, Eca-109, HepG2, BEL-7402, and normal NIH 3T3 cells were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) method. The results showed that the three iridium(III) complexes had moderate in vitro anti-tumor activity toward SGC-7901 cells with IC50 values of 3.6 ± 0.1 µM for >1, 14.1 ± 0.5 µM for >2, and 11.1 ± 1.3 µM for >3. Further studies showed that >1–>3 induce cell apoptosis/death through DNA damage, cell cycle arrest at the S or G0/G1 phase, ROS elevation, increased levels of Ca²⁺, high mitochondrial membrane depolarization, and cellular ATP depletion. Transwell and Colony-Forming assays revealed that complexes >1–>3 can also effectively inhibit the metastasis and proliferation of tumor cells. These results demonstrate that >1–>3 induce apoptosis in SGC-7901 cells through ROS-mediated mitochondrial damage and DNA damage pathways, as well as by inhibiting cell invasion, thereby exerting anti-tumor cell proliferation activity in vitro.