一组含有唑基配体框架的新型 Cu(II) 复合物的合成、表征和生物活性比较

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2024-09-19 DOI:10.1016/j.jinorgbio.2024.112736

Courtney E. Elwell , Emily Stein , Adam Lewis , Stefan Hamaway , Kennedy A. Alexis , Joseph M. Tanski , Timothy J. Barnum , Colleen M. Connelly , Laurie A. Tyler

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引用次数: 0

摘要

本研究报告了配体框架中含有取代的 2-(2-吡啶基)苯并噻唑（PyBTh）基团的三种配合物的合成、光谱特征以及生物活性比较。配体的 6 位被甲氧基（Py(OMe)BTh）或甲基（Py(Me)BTh）取代。Py(OMe)BTh与 CuCl2 或 Cu(NO3)2-2.5 H2O 反应分别产生单体[Cu(Py(OMe)BTh))2(NO3)]NO3-1.5 MeOH、(1-1.5 MeOH) 复合物或二聚体[Cu(Py(OMe)BTh)Cl2]2 (2)，复合物的核性取决于起始的 Cu(II) 盐。甲基取代配体与 Cu(NO3)2-2.5 H2O 反应后，分离出了 Cu(Py(Me)BTh)(NO3)2-0.5 THF（3-0.5 THF）。对 1-3 号配合物进行了全面表征。对所有这三种配合物以及[Cu(PyBTh)2(H2O)](BF4)2 (4)进行了循环伏安测量。研究的生物活性包括浓度依赖性 DNA 结合和裂解、抗菌活性和癌细胞毒性。所有复合物都具有 DNA 切割活性，但发现 2 和 4 的效力最强。机理研究表明，核酸酶活性主要依赖于 O2- 的氧化机制。抗菌研究表明，复合物 4 比 1-3 更有效。用 1-4、Cu(QBTh)(NO3)2(H2O) 和 Cu(PyBIm)3(BF4)2 对 HeLa、PC-3 和 MCF7 细胞进行了癌细胞毒性研究。观察到的毒性差异表明配体及其取代基在调节细胞死亡中的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthesis, characterization and comparative biological activity of a novel set of Cu(II) complexes containing azole-based ligand frames

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Synthesis, characterization and comparative biological activity of a novel set of Cu(II) complexes containing azole-based ligand frames

The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(OMe)BTh) or a methyl group (Py(Me)BTh). Reaction of Py(OMe)BTh with either CuCl₂ or Cu(NO₃)₂·2.5 H₂O yielded the monomeric [Cu(Py(OMe)BTh))₂(NO₃)]NO₃·1.5 MeOH, (1·1.5 MeOH) complex or the dimeric [Cu(Py(OMe)BTh)Cl₂]₂ (2), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO₃)₂·2.5 H₂O resulted in the isolation of Cu(Py(Me)BTh)(NO₃)₂·0.5 THF (3·0.5 THF). Complexes 1–3 were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)₂(H₂O)](BF₄)₂ (4), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however 2 and 4 were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O₂⁻. Antibacterial studies revealed complex 4 was more potent compared to 1–3. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with 1–4, Cu(QBTh)(NO₃)₂(H₂O) and Cu(PyBIm)₃(BF₄)₂. The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.

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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.