合成并表征了一种新的配体DFIP（2-(二苯并[b,d]呋喃-3-基)-1H-咪唑并[4,5-f][1,10]菲啰啉）及其两个配合物铱（III）[Ir(ppy)2(DFIP)](PF6)（ppy = 2-苯基吡啶，Ir1）和铑（II）[Ru(bpy)2(DFIP)](PF6)2（bpy = 2,2'-联吡啶，Ru1）。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物（MTT）方法测试了两个配合物对A549、BEL-7402、HepG2、SGC-7901、HCT116和正常LO2细胞的抗癌效果。Ir1在A549、BEL-7402、SGC-7901和HepG2上表现出高的细胞毒性活性，Ru1对A549、BEL-7402和SGC-7901细胞显示中等的抗癌活性。Ir1和Ru1对A549的IC50值分别为7.2 ± 0.1和22.6 ± 1.4 μM。研究了复合物Ir1和Ru1在线粒体中的定位、细胞内活性氧（ROS）水平的积累、线粒体膜电位（MMP）和细胞色素c（Cyt-C）的变化。通过流式细胞术检测细胞凋亡和细胞周期。使用共聚焦激光扫描显微镜检测Immunogenic cell death (ICD)对Ir1和Ru1在A549上的影响。通过Western Blotting检测凋亡相关蛋白的表达。Ir1和Ru1可以增加细胞内ROS水平和释放Cyt-C，降低MMP，导致A549细胞凋亡，并阻断A549细胞在G0/G1期。此外，复合物会降低聚苯乙烯-二醇酰辅酶A（PARP）、Caspase 3、Bcl-2（B细胞淋巴瘤-2）、PI3K（磷脂酰肌醇-3激酶）的表达并上调Bax的表达。所有这些发现表明，复合物通过Immunogenic cell death、凋亡和自噬诱导细胞死亡发挥抗癌效应。© 2023作者，独家授权生物无机化学学会（SBIC）。

A new ligand DFIP (2-(dibenzo[b,d]furan-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) and its two complexes iridium(III) [Ir(ppy)2(DFIP)](PF6) (ppy = 2-phenylpyridine, Ir1) and ruthenium(II) [Ru(bpy)2(DFIP)](PF6)2 (bpy = 2,2'-bipyridine, Ru1) were synthesized and characterized. The anticancer effects of the two complexes on A549, BEL-7402, HepG2, SGC-7901, HCT116 and normal LO2 cells were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex Ir1 shows high cytotoxic activity on A549, BEL-7402, SGC-7901 and HepG2, Ru1 exhibits moderate anticancer activity toward A549, BEL-7402 and SGC-7901 cells. The IC50 values of Ir1 and Ru1 toward A549 are 7.2 ± 0.1 and 22.6 ± 1.4 μM, respectively. The localization of complexes Ir1 and Ru1 in the mitochondrial, intracellular accumulation of reactive oxygen species (ROS) levels, and the changes of mitochondrial membrane potential (MMP) and cytochrome c (cyto-c) were investigated. Apoptosis and cell cycle were detected by flow cytometry. Immunogenic cell death (ICD) was used to detect the effects of Ir1 and Ru1 on the A549 using a confocal laser scanning microscope. The expression of apoptosis-related proteins was detected by western blotting. Ir1 and Ru1 can increase the intracellular ROS levels and release cyto-c, reduce the MMP, leading to the apoptosis of A549 cells and blocking the A549 cells at the G0/G1 phase. Additionally, the complexes caused a decrease of the expression of polyADP-ribose polymerase (PARP), caspase 3, Bcl-2 (B-cell lymphoma-2), PI3K (phosphoinositide-3 kinase) and upregulated the expression of Bax. All these findings indicated that the complexes exert anticancer efficacy to induce cell death through immunogenic cell death, apoptosis, and autophagy.© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).