首次合成和鉴定了两种新的一核铂（II）配位化合物，[Pt（L1）（DMSO）Cl]（PtL1）和[Pt（L2）（DMSO）Cl]（PtL2），它们与5-（乙氧基甲基）-8-羟基喹啉盐酸盐（H-L1）和5-溴-8-羟基喹啉（H-L2）配位。 对PtL1和PtL2的细胞毒性活性在健康的HL-7702细胞系和癌细胞系，人肺腺癌A549癌细胞和顺铂耐药的肺腺癌A549 / DDP肿瘤细胞（A549R）中进行了筛选，并与H-L1，H-L2，H-L3配体和8-羟基喹啉（H-L3）铂（II）配合物[Pt（L3）（DMSO）Cl]（PtL3）进行了比较。 MTT结果显示，对A549R进行一次脱质化L1配体的PtL1比PtL2和PtL3配合物更有效，效果提高了8.8-48.6倍，但对健康的HL-7702细胞更具选择性。此外，PtL1和PtL3通过显著诱导线粒体自噬并引起相关蛋白质表达的改变，从而导致细胞凋亡来克服肿瘤耐药性。此外，对A549异种移植肿瘤的抑制作用为68.2％，远高于顺铂（cisPt，约50.0％），而与未处理组相比，裸鼠体重并没有显著变化。本研究有助于探索新型Pt耐药癌症治疗的潜力。 版权所有©2023 Elsevier Inc.。

For the first time, two new mononuclear platinum(II) coordination compounds, [Pt(L1)(DMSO)Cl] (PtL1) and [Pt(L2)(DMSO)Cl] (PtL2) with the 5-(ethoxymethyl)-8-hydroxyquinoline hydrochloride (H-L1) and 5-bromo-8-hydroxyquinoline (H-L2) have been synthesized and characterized. The cytotoxic activity of PtL1 and PtL2 were screened in both healthy HL-7702 cell line and cancer cell lines, human lung adenocarcinoma A549 cancer cells and cisplatin-resistant lung adenocarcinoma A549/DDP cancer cells (A549R), and were compared to that of the H-L1, H-L2, H-L3 ligands and 8-hydroxyquinoline (H-L3) platinum(II) complex [Pt(L3)(DMSO)Cl] (PtL3). MTT results showed that PtL1 bearing one deprotonated L1 ligand against A549R was more potent by 8.8-48.6 fold than that of PtL2 and PtL3 complexes but was more selective toward healthy HL-7702 cells. In addition, PtL1 and PtL3 overcomes tumour drug resistance by significantly inducing mitophagy and causing the change of the related proteins expression, which leads to cell apoptosis. Moreover, the inhibitory effect of PtL1 on A549 xenograft tumour was 68.2%, which was much higher than that of cisplatin (cisPt, ca. 50.0%), without significantly changing nude mice weight in comparison with the untreated group. This study helps to explore the potential of the platinum(II) 5-substituted-8-hydroxyquinoline coordination compounds for the new Pt-resistant cancer therapy.Copyright © 2023 Elsevier Inc. All rights reserved.