钌(II/III)配位化合物作为化疗药物、光敏剂和光动力治疗试剂受到广泛关注。在此，一族 11 种新型香豆素配位 8-羟基喹啉钌(II/III) 化合物，即 [RuII2(μ2-Cl)2(QL1a)2(DMSO)4] (YNU-4a = 榆林师范大学-4a ), [RuII2(μ2-Cl)2(QL1b)2(DMSO)4] (YNU-4b), [RuII2(μ2-Cl)2(QL1c)2(DMSO)4] (YNU-4c), [RuII2 (μ2-Cl)2(QL1d)2(DMSO)4]·2CH3OH (YNU-4d), [RuII(QL1e)2(DMSO)2] (YNU-4e), [RuIII(QL1e)2(QL3a)] (YNU-4f)、[RuIII(QL1e)2(QL3b)] (YNU-4g)、[RuIII(QL1e)2(QL3c)] (YNU-4h)、[RuIICl2(H-QL3a)2(DMSO)2 ] (YNU-4i)、[RuIICl2(H-QL3b)2(DMSO)2] (YNU-4j) 和 [RuIICl2(H-QL3c)2(DMSO)2] (YNU-4k)，具有共配体 5 ,7-二碘-8-羟基喹啉 (H-QL1a)、5,7-二氯-8-羟基喹啉 (H-QL1b)、5-氯-7-碘-8-羟基喹啉 (H-QL1c)、5,7-二溴-8-羟基喹啉 (H-QL1d) 和 5,7-二氯-8-羟基-2-甲基喹啉 (H-QL1e) 以及主要配体 6,7-二氯-3-吡啶-2-基-苯并呋喃- 2-酮 (H-QL3a)、6-溴-3-吡啶-2-基-苯并-2-酮 (H-QL3b) 和 6-氯-3-吡啶-2-基-苯-2-酮(H-QL3c)，分别。通过各种光谱分析充分证实了化合物YNU-4a-YNU-4k的结构。在顺铂耐药的 A549/DDP 肺癌细胞 (LC549) 与正常胚胎肾 (HEK293) 细胞中评估了 YNU-4a-YNU-4k 的抗癌活性。值得注意的是，与 YNU-4a-YNU-4e、H-QL1a-H 相比，带有 QL1e 和 QL3a 配体的化合物 YNU-4f 对 LC549 细胞表现出更明显的抗增殖作用 (IC50 = 1.75 ± 0.09 μM)，对 LC549 癌细胞具有高内在选择性-QL1e、顺铂 (PDD)、YNU-4g-YNU-4k 和 H-QL3a-H-QL3c。此外，YNU-4e 和 YNU-4f 的共定位分析表明，这两种钌 (II/III) 化合物在线粒体和细胞质的其他区域进行亚细胞积累，在那里它们诱导线粒体自噬、三磷酸腺苷 (ATP) 还原、线粒体呼吸链复合物 I/IV (RC1/RC4) 抑制和线粒体功能障碍。因此，化合物YNU-4a-YNU-4k可被视为线粒体自噬诱导剂，用于根除顺铂耐药的LC549癌细胞。版权所有©2023。由Elsevier Inc.出版。

Ruthenium(II/III) coordination compounds have gained widespread attention as chemotherapy drugs, photosensitizers, and photodynamic therapy reagents. Herein, a family of 11 novel coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds, i.e., [RuII2(μ2-Cl)2(QL1a)2(DMSO)4] (YNU-4a = Yulin Normal University-4a), [RuII2(μ2-Cl)2(QL1b)2(DMSO)4] (YNU-4b), [RuII2(μ2-Cl)2(QL1c)2(DMSO)4] (YNU-4c), [RuII2(μ2-Cl)2(QL1d)2(DMSO)4]⋅2CH3OH (YNU-4d), [RuII(QL1e)2(DMSO)2] (YNU-4e), [RuIII(QL1e)2(QL3a)] (YNU-4f), [RuIII(QL1e)2(QL3b)] (YNU-4g), [RuIII(QL1e)2(QL3c)] (YNU-4h), [RuIICl2(H-QL3a)2(DMSO)2] (YNU-4i), [RuIICl2(H-QL3b)2(DMSO)2] (YNU-4j), and [RuIICl2(H-QL3c)2(DMSO)2] (YNU-4k), featuring the coligands 5,7-diiodo-8-hydroxyquinoline (H-QL1a), 5,7-dichloro-8-quinolinol (H-QL1b), 5-chloro-7-iodo-8-hydroxyquinolin (H-QL1c), 5,7-dibromo-8-hydroxyquinoline (H-QL1d), and 5,7-dichloro-8-hydroxy-2-methylquinoline (H-QL1e) and the main ligands 6,7-dichloro-3-pyridin-2-yl-chromen-2-one (H-QL3a), 6-bromo-3-pyridin-2-yl-chromen-2-one (H-QL3b), and 6-chloro-3-pyridin-2-yl-chromen-2-one (H-QL3c), respectively. The structure of compounds YNU-4a-YNU-4k was fully confirmed by conducting various spectroscopic analyses. The anticancer activity of YNU-4a-YNU-4k was evaluated in cisplatin-resistant A549/DDP lung cancer cells (LC549) versus normal embryonic kidney (HEK293) cells. Notably, compound YNU-4f bearing QL1e and QL3a ligands showed a more pronounced antiproliferative effect against LC549 cells (IC50 = 1.75 ± 0.09 μM) with high intrinsic selectivity toward LC549 cancer cells than YNU-4a-YNU-4e, H-QL1a-H-QL1e, cisplatin (PDD), YNU-4g-YNU-4k, and H-QL3a-H-QL3c. Additionally, a colocalization assay analysis of YNU-4e and YNU-4f showed that these two ruthenium(II/III) compounds were subcellularly accumulated in the mitochondria and other regions of the cytoplasm, where they induce mitophagy, adenosine triphosphate (ATP) reduction, mitochondrial respiratory chain complex I/IV(RC1/RC4) inhibition, and mitochondrial dysfunction. Accordingly, compounds YNU-4a-YNU-4k can be regarded as mitophagy inductors for the eradication of cisplatin-resistant LC549 cancer cells.Copyright © 2023. Published by Elsevier Inc.