基于8-羟基喹啉的六种新型双核钙（II）配合物抗癌作用的研究

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2025-09-04 DOI:10.1016/j.jinorgbio.2025.113055

Xiao-Mei Huang , Yue Xu , Si-Mei Qin , Ming-Xiong Tan , Qi-Pin Qin , Tai-Ming Shao , Hong Liang

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The specific compositions are as follows: CaQ1: H-QM1 = 5,7-dibromo-8-hydroxyquinoline (x = 1), QH1 = bathophenanthroline; CaQ2: H-QM2 = 5,7-dichloro-8-quinolinol (x = 2), QH1 = bathophenanthroline; CaQ3: H-QM3 = 5,7-diiodo-8-hydroxyquinoline (x = 3), QH2 = 1,10-phenanthroline; CaQ4: H-QM2 = 5,7-dichloro-8-quinolinol (x = 2), QH2 = 1,10-phenanthroline; CaQ5: H-QM4 = clioquinol (x = 4), QH2 = 1,10-phenanthroline; CaQ6: H-QM1 = 5,7-dibromo-8-hydroxyquinoline (x = 1), QH2 = 1,10-phenanthroline. Cytotoxicity was assessed using the cell counting kit-8 assay, and the results showed that CaQ1–CaQ6 exhibited greater selectivity toward cisplatin-resistant SK-OV-3/DDP ovarian (cis-SK3) cancer cells compared to both nontumorigenic HL-7702 liver cells and parental SK-OV-3 ovarian cancer cells. 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引用次数: 0

摘要

本研究报道了六种新型双核钙（II）配合物的合成和抗肿瘤评价，其通式为[Ca2(μ2-O)2(QMx)4(QHy)2]，编号为CaQ1 ~ CaQ6。这些配合物包含各种去质子化的8-羟基喹啉配体（H-QM1−H-QM4）和1,10-菲罗啉衍生物（QH2），由Ca(NO3)2·4H2O合成。具体组成如下：CaQ1: H-QM1 = 5,7-二溴-8-羟基喹啉（x = 1）， QH1 =邻苯二酚；CaQ2: H-QM2 = 5,7-二氯-8-喹啉（x = 2）， QH1 =邻苯二酚；CaQ3: H-QM3 = 5,7-二碘-8-羟基喹啉（x = 3）， QH2 = 1,10-菲罗啉；CaQ4: H-QM2 = 5,7-二氯-8-喹啉（x = 2）， QH2 = 1,10-菲罗啉；CaQ5: H-QM4 = clioquinol (x = 4), QH2 = 1,10-菲罗啉；CaQ6: H-QM1 = 5,7-二溴-8-羟基喹啉（x = 1）， QH2 = 1,10-菲罗啉。使用细胞计数试剂盒-8法评估细胞毒性，结果显示，与非致瘤性HL-7702肝细胞和亲代SK-OV-3卵巢癌细胞相比，CaQ1-CaQ6对顺铂耐药的SK-OV-3/DDP卵巢癌细胞（顺- sk3）具有更高的选择性。值得注意的是，含有活性H-QM1、H-QM2和QH1配体的CaQ1和CaQ2对顺式sk3细胞的IC50值分别为3.59±0.67 μM和2.73±0.25 μM，显示出最强的细胞毒性。CaQ1和CaQ2诱导的细胞凋亡是通过线粒体自噬激活和三磷酸腺苷耗散介导的，CaQ2比CaQ1更有效，可能是由于CaQ2复合体中存在QM2和QH1配体。综上所述，这些发现表明合成的8-羟基喹啉双核钙(II)-1,10-菲罗啉配合物（CaQ1−CaQ6）是很有前途的Ca（II）基抗癌药物候选物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Development of six novel dinuclear calcium(II) complexes based on 8-hydroxyquinoline as anticancer agents

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Development of six novel dinuclear calcium(II) complexes based on 8-hydroxyquinoline as anticancer agents

This study reports the synthesis and antitumor evaluation of six novel dinuclear calcium(II) complexes with the general formula [Ca₂(μ₂-O)₂(QM^x)₄(QH^y)₂], designated as CaQ1 through CaQ6. These complexes incorporate various deprotonated 8-hydroxyquinoline ligands (H-QM¹−H-QM⁴) and 1,10-phenanthroline derivatives (QH²), synthesized using Ca(NO₃)₂·4H₂O. The specific compositions are as follows: CaQ1: H-QM¹ = 5,7-dibromo-8-hydroxyquinoline (x = 1), QH¹ = bathophenanthroline; CaQ2: H-QM² = 5,7-dichloro-8-quinolinol (x = 2), QH¹ = bathophenanthroline; CaQ3: H-QM³ = 5,7-diiodo-8-hydroxyquinoline (x = 3), QH² = 1,10-phenanthroline; CaQ4: H-QM² = 5,7-dichloro-8-quinolinol (x = 2), QH² = 1,10-phenanthroline; CaQ5: H-QM⁴ = clioquinol (x = 4), QH² = 1,10-phenanthroline; CaQ6: H-QM¹ = 5,7-dibromo-8-hydroxyquinoline (x = 1), QH² = 1,10-phenanthroline. Cytotoxicity was assessed using the cell counting kit-8 assay, and the results showed that CaQ1–CaQ6 exhibited greater selectivity toward cisplatin-resistant SK-OV-3/DDP ovarian (cis-SK3) cancer cells compared to both nontumorigenic HL-7702 liver cells and parental SK-OV-3 ovarian cancer cells. Notably, CaQ1 and CaQ2, which contain the active H-QM¹, H-QM², and QH¹ ligands, showed the most potent cytotoxicity, with IC₅₀ values of 3.59 ± 0.67 μM and 2.73 ± 0.25 μM, respectively, against cis-SK3 cells. Apoptosis induced by CaQ1 and CaQ2 was mediated by mitophagy activation and adenosine triphosphate depletion, with CaQ2 being more effective than CaQ1—likely due to the presence of QM² and QH¹ ligands in the CaQ2 complex. In conclusion, these findings suggest that the synthesized 8-hydroxyquinoline-based binuclear calcium(II)-1,10-phenanthroline complexes (CaQ1−CaQ6) represent promising Ca(II)-based anticancer drug candidates.

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.