三种新型的与5,7-二卤-8-喹啉酸的双核钙（II）配合物显示出有效的抗癌活性

IF 3.3 3区化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR

Dalton Transactions Pub Date : 2025-08-14 DOI:10.1039/D5DT01456E

Si-Mei Qin, Yue Xu, Xiao-Mei Huang, Ming-Xiong Tan, Qing-Min Wei, Zhi-Hui Luo, Hong Liang and Qi-Pin Qin

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引用次数: 0

摘要

为了开发克服顺铂（RiPt）耐药性的新型钙（II）配位化合物，我们合成了三种双核钙（II）配合物：[Ca2(μ2-O)2(dhg1)4(CP)2] （CaL1）、[Ca2(μ2-O)2(dhg2)4(CP)2] （CaL2）和[Ca2(μ2-O)2(dhg3)4(CP)2] （CaL3）。它们分别含有四种去质子化的5,7-二氯-8-喹啉（H-dhg1）、氯喹啉（H-dhg2）或5,7-二溴-8-羟基喹啉（H-dhg3）配体和两种5-氯-1,10-菲罗啉（CP）配体。CaL1-CaL3对顺铂耐药卵巢SK-OV-3/DDP （RiSK3）癌细胞和健康（HL-7702）细胞的体外细胞毒性研究显示，CaL1-CaL3对RiSK3细胞具有选择性细胞毒性，IC50分别为0.58±0.03 μM、0.89±0.12 μM和1.93±0.26 μM。值得注意的是，CaL1和CaL2不仅能诱导RiSK3细胞凋亡，还能诱导致死性的有丝分裂。这些发现为开发能够克服RiPt耐药的钙(II) - 8-羟基喹啉类药物提供了一个有希望的策略。

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Three novel dinuclear calcium(ii) complexes with 5,7-dihalo-8-quinolinolato showing potent anticancer activity

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Three novel dinuclear calcium(ii) complexes with 5,7-dihalo-8-quinolinolato showing potent anticancer activity

To develop novel calcium(II) coordination compounds aimed at overcoming cisplatin (RiPt) resistance, we synthesized three dinuclear calcium(II) complexes: [Ca₂(μ₂-O)₂(dhg1)₄(CP)₂] (CaL1), [Ca₂(μ₂-O)₂(dhg2)₄(CP)₂] (CaL2), and [Ca₂(μ₂-O)₂(dhg3)₄(CP)₂] (CaL3). These contain four deprotonated 5,7-dichloro-8-quinolinol (H-dhg1), clioquinol (H-dhg2), or 5,7-dibromo-8-hydroxyquinoline (H-dhg3) ligands, respectively, and two 5-chloro-1,10-phenanthroline (CP) ligands. In vitro cytotoxicity studies of CaL1–CaL3 against cisplatin-resistant ovarian SK-OV-3/DDP (RiSK3) cancer cells and healthy (HL-7702) cells revealed promising selective cytotoxicity toward RiSK3 cells with IC₅₀ values of 0.58 ± 0.03, 0.89 ± 0.12 and 1.93 ± 0.26 μM, respectively. Notably, CaL1 and CaL2 induced not only apoptosis but also lethal mitophagy in RiSK3 cells. These findings provide a promising strategy for developing calcium(II)-8-hydroxyquinoline-based drugs capable of overcoming RiPt resistance.

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来源期刊

Dalton Transactions 化学-无机化学与核化学

CiteScore

6.60

自引率

7.50%

发文量

1832

审稿时长

1.5 months

期刊介绍： Dalton Transactions is a journal for all areas of inorganic chemistry, which encompasses the organometallic, bioinorganic and materials chemistry of the elements, with applications including synthesis, catalysis, energy conversion/storage, electrical devices and medicine. Dalton Transactions welcomes high-quality, original submissions in all of these areas and more, where the advancement of knowledge in inorganic chemistry is significant.