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一种源自5-氟尿嘧啶的新型席夫碱及其M(II)配合物的合成、表征、抗氧化和抗癌活性

Synthesis, characterization, antioxidant and anticancer activities of a new Schiff base and its M(II) complexes derived from 5-fluorouracil.

作者信息

Savcı Ahmet, Buldurun Kenan, Alkış Mehmet Eşref, Alan Yusuf, Turan Nevin

机构信息

Department of Molecular Biology and Genetics, Faculty of Art and Science, Mus Alparslan University, 49250, Mus, Turkey.

Department of Medical Services and Techniques, Health Services Vocational School, Mus Alparslan University, 49250, Mus, Turkey.

出版信息

Med Oncol. 2022 Aug 16;39(11):172. doi: 10.1007/s12032-022-01774-0.

Abstract

In this study, Schiff base ligand was obtained from the condensation reaction of benzene-1,2-diamine and 5-fluoropyrimidine-2,4(1H,3H)-dione (5-FU). Metal(II) complexes were synthesized with Fe(II), Co(II) and Ni(II) chloride salts. The synthesized ligand and metal complexes were characterized by FT-IR, UV-vis, H-C NMR, elemental analyses, mass spectroscopy, magnetic moments, molar conductivity and thermogravimetric analysis studies. With the help of different techniques reveal Fe(II), Co(II) and Ni(II) complexes have exhibited tetrahedral and octahedral geometry. Ligand acted as bidentate and it binds metal(II) ions through deprotonated-NH, imine-N atom and carbonyl-O atom, respectively. DPPH, ABTS, FRAP, CUPRAC and total antioxidant activity methods were used to determine the antioxidant properties of ligand and metal complexes. According to the results, the synthesized compounds showed very high antioxidant activity compared to 5-FU. The cytotoxicities of the synthesized compounds were performed on MCF-7 (human breast cancer) and L-929 (fibroblast) cell lines using the MTT assay. In addition, the effect of electroporation (EP) on the cytotoxicity of the compounds was investigated. Our results demonstrated that novel Co(II) and Ni(II) complexes show potential as new anticancer agents and ECT may be a viable treatment option for breast cancer.

摘要

在本研究中,席夫碱配体由苯 - 1,2 - 二胺与5 - 氟嘧啶 - 2,4(1H,3H) - 二酮(5 - FU)的缩合反应制得。用氯化铁(II)、氯化钴(II)和氯化镍(II)合成了金属(II)配合物。通过傅里叶变换红外光谱(FT - IR)、紫外 - 可见光谱(UV - vis)、氢核磁共振(H - C NMR)、元素分析、质谱、磁矩、摩尔电导率和热重分析研究对合成的配体和金属配合物进行了表征。借助不同技术表明,铁(II)、钴(II)和镍(II)配合物呈现四面体和八面体几何构型。配体作为双齿配体,分别通过去质子化的 - NH、亚胺 - N原子和羰基 - O原子与金属(II)离子结合。采用二苯基苦味酰基自由基(DPPH)、2,2'-联氮 - 双 - 3 - 乙基苯并噻唑啉 - 6 - 磺酸(ABTS)、铁离子还原抗氧化能力(FRAP)、铜离子还原抗氧化能力(CUPRAC)和总抗氧化活性方法来测定配体和金属配合物的抗氧化性能。结果表明,与5 - FU相比,合成的化合物表现出非常高的抗氧化活性。使用MTT法对合成化合物在MCF - 7(人乳腺癌)和L - 929(成纤维细胞)细胞系上进行细胞毒性测试。此外,研究了电穿孔(EP)对化合物细胞毒性的影响。我们的结果表明,新型钴(II)和镍(II)配合物显示出作为新型抗癌剂的潜力,并且电穿孔疗法(ECT)可能是乳腺癌的一种可行治疗选择。

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