钌配合物和8-喹啉类化合物已被提出作为恶性肿瘤治疗的潜在新药。本文合成、表征并测试了三种三苯基膦钌配合物[Ru(ZW1)(PPh3)2Cl2]（PPh3 = 三苯基膦）（RuZ1）、[Ru(ZW2)(PPh3)2Cl2]（RuZ2）和[Ru(ZW2)2(PPh3)Cl2]·CH2Cl2（RuZ3），其中配体为5,7-二氯-8-喹啉酮（H-ZW1）和5,7-二氯-8-羟基喹啉醛（H-ZW2），并评估了它们的抗癌潜力。结果显示，三苯基膦钌配合物RuZ1-RuZ3比顺铂对卵巢腺癌顺铂耐药SK-OV-3/DDP（SKO3CR）和SK-OV-3（SKO3）癌细胞的细胞活力具有更高的选择性和特异性。此外，RuZ1-RuZ3对SKO3CR细胞的细胞毒性优于顺铂，其IC50值分别为9.66 ± 1.08、4.05 ± 0.67和7.18 ± 0.40 μM，其中SKO3CR细胞对RuZ1-RuZ3最为敏感。根据取代基类型，RuZ1-RuZ3的抗增殖能力的顺序为：-CH3 > -H。然而，RuZ1-RuZ3对正常细胞HL-7702无明显毒性。此外，RuZ1和RuZ2能够通过抑制线粒体内质膜电位（ΔΨm）的降低、[Ca2+]和活性氧（ROS）的积累、LC3 II/LC3 I、Beclin-1、P62、FUNDC1、PINK1、Parkin、剪切的caspase-3、caspase-9和细胞色素c信号通路的调控，以及抑制线粒体呼吸链复合物I和IV及ATP水平的制备，诱导线粒体自噬凋亡通路。机制研究揭示了RuZ1和RuZ2通过诱导线粒体自噬凋亡通路和干扰能量（ATP）产生而诱导SKO3CR细胞凋亡。综上所述，研究中的三苯基膦钌配合物RuZ1-RuZ3是具有高效性和低毒性的有希望的化疗药物。版权所有 © 2023，Elsevier Inc.发表。

Both ruthenium-containing complexes and 8-quinolinoline compounds have emerged as a potential novel agent for malignant tumor therapy. Here, three triphenylphosphine ruthenium complexes, [Ru(ZW1)(PPh3)2Cl2] (PPh3 = triphenylphosphine) (RuZ1), [Ru(ZW2)(PPh3)2Cl2] (RuZ2) and [Ru(ZW2)2(PPh3)Cl2]·CH2Cl2 (RuZ3) bearing 5,7-dichloro-8-quinolinol (H-ZW1) and 5,7-dichloro-8-hydroxyquinaldine (H-ZW2), have been synthesized, characterized and tested for their anticancer potential. We showed that triphenylphosphine ruthenium complexes RuZ1-RuZ3 impaired the cell viability of ovarian adenocarcinoma cisplatin-resistant SK-OV-3/DDP (SKO3CR) and SK-OV-3 (SKO3) cancer cells with greater selectivity and specificity than cisplatin. In addition, RuZ1-RuZ3 show higher excellent cytotoxicity than cisplatin towards SKO3CR cells, with IC50 values of 9.66 ± 1.08, 4.05 ± 0.67 and 7.18 ± 0.40 μM, respectively, in which the SKO3CR cells was the most sensitive to RuZ1-RuZ3. Depending on the substituent type, the antiproliferative ability of RuZ1-RuZ3 followed the trend: -CH3 > -H. However, RuZ1-RuZ3 have no obvious toxicity to normal cell HL-7702. Besides, RuZ1 and RuZ2 could induce mitophagy related-apoptosis pathways through suppression of mitochondrial membrane potential (ΔΨm), accumulation of [Ca2+] and reactive oxygen species (ROS), and regulation of LC3 II/LC3 I, Beclin-1, P62, FUNDC1, PINK1, Parkin, cleaved-caspase-3, caspase-9 and cytochrome c signaling pathway, and hindering the preparation of mitochondrial respiration complexes I and IV and ATP levels. Mechanistic study revealed that RuZ1 and RuZ2 induce apoptosis in SKO3CR cells via mitophagy related-apoptosis pathways induction and energy (ATP) generation disturbance. Taken together, the studied triphenylphosphine ruthenium complexes RuZ1-RuZ3 are promising chemotherapeutic agents with high effectiveness and low toxicity.Copyright © 2023. Published by Elsevier Inc.