In this report, we synthesized three new iridium(III) complexes: [Ir(piq)₂(apip)]PF₆ (Ir1, piq = 1-phenylisoquinoline, apip = 2-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(piq)₂(maip)]PF₆ (Ir2, maip = 3-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(piq)₂(paip)]PF₆ (Ir3, paip = 4-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline). The DNA binding was investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the cytotoxic activity of Ir1, Ir2 and Ir3, the complexes show highly active against B16 cells with IC₅₀ values of 0.3 ± 0.2 μM, 3.7 ± 0.2 μM and 4.6 ± 1.1 μM, respectively. Subsequently, cellular uptake suggested that the cytotoxicity of the complexes is attributed to their differences in cellular uptake levels. In addition, complexes Ir1, Ir2 and Ir3 induce cell cycle arrest at the G0/G1 phase and regulate the cell cycle mediators such as cyclin D1, CDK6 (cyclin-dependent kinase 6), CDK4 and p21, leading to the inhibition of B16 cells proliferation. The autophagy was investigated by monodansylcadaverine (MDC) staining. The complexes can promote the change from LC3-I to LC3-II, up-regulate levels of Beclin-1 and down-regulate expression of p62. The complexes induced apoptosis by regulating the expression levels of related indicators such as PARP (poly ADP-ribose polymerase), PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), Caspase, Bcl-2 (B-cell lymphoma-2), Bad (Bcl2 associated death promoter), Bax (Bcl2-associated X) and Cyto C (cytochrome C). Additionally, Ir1 exerted significant antitumor activity in the suppression of malignant melanoma proliferation in vivo. As indicated in the above results, these complexes were highly effective for malignant melanoma treatment through the intrinsic pathway and provided much insight into anticancer drugs for tumor therapy.

在本报告中，我们合成了三种新的铱（III）配合物：[Ir(piq) ₂ (apip)]PF ₆ ( Ir1 , piq = 1-phenylisoquinoline, aip = 2-aminophenyl-1 H -imidazo [4,5- f][1,10]菲咯啉）、[Ir(piq) ₂ (maip)]PF ₆ ( Ir2 , maip = 3-aminophenyl-1 H -imidazo [4,5-f][1,10]phenanthroline) 和[Ir(piq) ₂ (paip)]PF ₆ ( Ir3 , paip = 4-氨基苯基-1 H-咪唑[4,5-f][1,10]菲咯啉)。研究了DNA结合。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)法检测Ir1的细胞毒活性、Ir2和Ir3，复合物对 B16 细胞表现出高度活性，IC ₅₀值分别为 0.3 ± 0.2 μM、3.7 ± 0.2 μM 和 4.6 ± 1.1 μM。随后，细胞摄取表明复合物的细胞毒性归因于它们在细胞摄取水平上的差异。此外，配合物Ir1、Ir2和Ir3诱导细胞周期停滞在 G0/G1 期并调节细胞周期介质，如细胞周期蛋白 D1、CDK6（细胞周期蛋白依赖性激酶 6）、CDK4 和 p21，从而抑制 B16 细胞增殖。通过单丹磺酰尸胺 (MDC) 染色研究自噬。该复合物可以促进LC3-I向LC3-II的转变，上调Beclin-1的水平，下调p62的表达。复合物通过调节PARP（聚ADP-核糖聚合酶）、PI3K（磷酸肌醇3激酶）、AKT（蛋白激酶B）、Caspase、Bcl-2（B细胞淋巴瘤2）等相关指标的表达水平诱导细胞凋亡)、Bad (Bcl2 相关死亡启动子)、Bax (Bcl2 相关 X) 和 Cyto C (细胞色素 C)。此外，Ir1在体内抑制恶性黑色素瘤增殖方面发挥显着的抗肿瘤活性。如上述结果所示，这些复合物通过内在途径对恶性黑色素瘤治疗非常有效，并为肿瘤治疗的抗癌药物提供了很多见解。