Kehua Wang , Ling Wang , Zhuye Shang , Xingzhi Yang , Hongmei Li , Xiaochun Wang , Mingchang Zhu , Qingtao Meng
{"title":"A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity","authors":"Kehua Wang , Ling Wang , Zhuye Shang , Xingzhi Yang , Hongmei Li , Xiaochun Wang , Mingchang Zhu , Qingtao Meng","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}
引用次数: 0
Abstract
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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