{"title":"一系列含有 1,8-萘二甲酰亚胺配体的 DNA 靶向 Cu (II) 复合物：合成、表征和体外抗癌活性","authors":"","doi":"10.1016/j.jinorgbio.2024.112721","DOIUrl":null,"url":null,"abstract":"<div><p>Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (<strong>1</strong>–<strong>3</strong>) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex <strong>3</strong>). In addition, a control compound (complex <strong>4</strong>) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes <strong>1</strong>–<strong>3</strong> was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order <strong>3</strong> > <strong>2</strong> > <strong>1</strong>, giving the IC<sub>50</sub> values ranging from 2.874 ± 0.155 μM to 31.47 ± 0.29 μM against five cancer cell lines. Complex <strong>4</strong> showed less activity in comparison with complex <strong>1</strong>–<strong>3</strong>. Notably, complexes <strong>1</strong>–<strong>3</strong> displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex <strong>4</strong> (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound <strong>3</strong> induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes <strong>3</strong> and <strong>4</strong> was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex <strong>3</strong> interacted with DNA in an intercalating mode, but the interaction mode of compound <strong>4</strong> with DNA was electrostatic interaction.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity\",\"authors\":\"\",\"doi\":\"10.1016/j.jinorgbio.2024.112721\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (<strong>1</strong>–<strong>3</strong>) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex <strong>3</strong>). In addition, a control compound (complex <strong>4</strong>) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes <strong>1</strong>–<strong>3</strong> was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order <strong>3</strong> > <strong>2</strong> > <strong>1</strong>, giving the IC<sub>50</sub> values ranging from 2.874 ± 0.155 μM to 31.47 ± 0.29 μM against five cancer cell lines. Complex <strong>4</strong> showed less activity in comparison with complex <strong>1</strong>–<strong>3</strong>. Notably, complexes <strong>1</strong>–<strong>3</strong> displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex <strong>4</strong> (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound <strong>3</strong> induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes <strong>3</strong> and <strong>4</strong> was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex <strong>3</strong> interacted with DNA in an intercalating mode, but the interaction mode of compound <strong>4</strong> with DNA was electrostatic interaction.</p></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013424002459\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013424002459","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
铜（II）配合物是非常有前途的铂类抗癌剂候选化合物。本文合成了三种含有 1,8-萘二甲酰亚胺配体的铜（II）配合物（1-3），并通过傅立叶变换红外光谱、元素分析、ESI-MS 和单晶 X 射线衍射对其进行了表征（配合物 3）。此外，还合成并表征了不含 1,8-萘二甲酰亚胺配体的对照化合物（复合物 4）。通过 MTS 试验评估了合成的复合物对五种癌细胞株和一种正常细胞株的体外抗癌活性。结果表明，复合物 1-3 的抗肿瘤活性受配体脂肪族链长度的控制，其细胞毒性依次为 3 > 2 > 1，对五种癌细胞株的 IC50 值为 2.874 ± 0.155 μM 至 31.47 ± 0.29 μM。与复合物 1-3 相比，复合物 4 的活性较低。值得注意的是，与复合物 4（SI = 1.0）相比，复合物 1-3 显示出更高的选择性（SI = 2.65 至 10.16），这表明引入 1,8-萘二甲酰亚胺基团不仅提高了该系列化合物的活性，还增强了它们对癌细胞的特异选择性。化合物 3 能诱导癌细胞凋亡，阻断癌细胞的 S 期和 G2/M。通过紫外/可见光谱滴定、竞争性 DNA 结合实验、粘度计和 CD 光谱研究了复合物 3 和 4 与 DNA 的相互作用。结果表明，复合物 3 与 DNA 的相互作用模式为插层作用，而化合物 4 与 DNA 的相互作用模式为静电作用。
A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity
Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (1–3) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex 3). In addition, a control compound (complex 4) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes 1–3 was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order 3 > 2 > 1, giving the IC50 values ranging from 2.874 ± 0.155 μM to 31.47 ± 0.29 μM against five cancer cell lines. Complex 4 showed less activity in comparison with complex 1–3. Notably, complexes 1–3 displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex 4 (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound 3 induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes 3 and 4 was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex 3 interacted with DNA in an intercalating mode, but the interaction mode of compound 4 with DNA was electrostatic interaction.
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.
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