The new ligand BBIP (BBIP = 2-(7-bromo-2H-benzo[d]imidazole-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) with its iridium(III) complexes: [Ir(ppy)₂(BBIP)](PF₆) (ppy = 2-phenylpyridine, Ir1), [Ir(bzq)₂(BBIP)](PF₆) (bzq = benzo[h]quinolone, Ir2) and [Ir(piq)₂(BBIP)](PF₆) (piq = 1-phenylisoquinoline, Ir3) were synthesized and characterized by elemental analysis, High Resolution Mass Spectrometer (HRMS), ¹H NMR and ¹³C{1H} NMR. The cytotoxicity of the complexes against A549, HepG2, SGC-7901, BEL-7402, HeLa and normal LO2 was evaluated through 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. The results show that Ir1 exhibits high cytotoxic activity against A549 cells with a low IC₅₀ value of 4.9 ± 0.5 μM. A series of biological activities such as cell cycle arrest, endoplasmic reticulum localization assay, apoptosis, western blotting, cellular uptake determination and in vivo antitumor activity were investigated. The assays implied that the complexes inhibit cancer cell migration through blocking mitotic progress. Cell cycle distribution stated that the complexes depress cell growth at G0/G1 phase. Additionally, the complexes acted on the endoplasmic reticulum and induce apoptosis through endoplasmic reticulum stress pathway. Especially, the western blotting showed that the complexes activated Bcl-2 (B-cell lymphoma-2) family and decreased PI3K (phosphoinositide-3 kinase) and AKT (protein kinase B), up-regulated the expression of mTOR (mammalian target of rapamycin) and p-mTOR (phosphorylated mammalian target of rapamycin). Therefore, the complexes induce apoptosis through activating PI3K-AKT-mTOR pathway. Antitumor in vivo demonstrated that Ir1 can effectively prevent the tumor growth with an inhibitory rate of 48.89%.

新配体 BBIP (BBIP = 2-(7-bromo-2 H -苯并[ d ]咪唑-4-基)-1 H -咪唑并[4,5- f ][1,10]菲咯啉)及其铱( III) 配合物：[Ir(ppy) ₂ (BBIP)](PF ₆ ) (ppy = 2-苯基吡啶, Ir1 ), [Ir(bzq) ₂ (BBIP)](PF ₆ ) (bzq = 苯并[ h ]喹诺酮, Ir2 ) 和 [Ir(piq) ₂ (BBIP)](PF ₆ ) (piq = 1-苯基异喹啉, Ir3 ) 被合成并通过元素分析、高分辨率质谱仪 (HRMS)、 ¹ H NMR 和¹³ C{ 进行表征。 1H}核磁共振。通过3-(4,5-二甲基噻唑-2-基)-2,5-联苯四唑溴化物(MTT)法评价复合物对A549、HepG2、SGC-7901、BEL-7402、HeLa和正常LO2的细胞毒性。 。结果表明， Ir1对 A549 细胞表现出高细胞毒活性，IC ₅₀值较低，为 4.9 ± 0.5 μM。研究了细胞周期阻滞、内质网定位测定、细胞凋亡、蛋白质印迹、细胞摄取测定和体内抗肿瘤活性等一系列生物学活性。分析表明，这些复合物通过阻止有丝分裂进程来抑制癌细胞迁移。细胞周期分布表明复合物抑制 G0/G1 期细胞生长。此外，复合物作用于内质网并通过内质网应激途径诱导细胞凋亡。 特别是，蛋白质印迹显示，复合物激活 Bcl-2（B 细胞淋巴瘤-2）家族，降低 PI3K（磷酸肌醇 3 激酶）和 AKT（蛋白激酶 B），上调 mTOR（哺乳动物靶标）的表达。雷帕霉素）和 p-mTOR（雷帕霉素的磷酸化哺乳动物靶标）。因此，复合物通过激活PI3K-AKT-mTOR途径诱导细胞凋亡。体内抗肿瘤实验表明Ir1能有效阻止肿瘤生长，抑制率为48.89%。