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新型 4-(芳基杂原子)-1H-吡唑配体 Cu(II)配合物的合成、表征、抗氧化活性和细胞毒性筛选。

Synthesis, characterization, antioxidant potential, and cytotoxicity screening of new Cu(II) complexes with 4-(arylchalcogenyl)-1H-pyrazoles ligands.

机构信息

Department of Basic Health Sciences - Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.

Center of Chemical, Pharmaceutical and Food Science Center, Group of Catalysis of Theoretical Studies, Federal University of Pelotas (UFPel), Pelotas, RS, Brazil.

出版信息

J Inorg Biochem. 2022 Dec;237:112013. doi: 10.1016/j.jinorgbio.2022.112013. Epub 2022 Sep 22.

Abstract

Two new Cu(II) complexes based on 4-(arylchalcogenyl)-1H-pyrazoles monodentate bis(ligand) containing selenium or sulfur groups (2a and 2b) have been synthesized and characterized by IR spectroscopy, high-resolution mass spectrometry (HRMS), and by X-ray crystallography. In the effort to propose new applications for the biomedical area, we evaluated the antioxidant activity and cytotoxicity of the newly synthesized complexes. The antioxidant activity of the Cu(II) complexes (2a - 2b) were assessed through their ability to inhibit the formation of reactive species (RS) induced by sodium azide and to scavenge the synthetic radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Both copper complexes containing selenium (2a) and sulfur (2b) presented in vitro antioxidant activity. The (1a - 1b and 2a - 2b) compounds did not show cytotoxicity in V79 cells at low concentrations. Furthermore, the antiproliferative activity of free ligands (1a - 1b) and their complexes (2a - 2b) were tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and HepG2 (hepatocarcinoma). Also, 2a was tested against U2OS (osteosarcoma). Our results demonstrated that 1a and 1b show little or no growth inhibition activities on human cell lines.The 2a compound exhibited good cytotoxic activity toward human tumor cell lines. However, 2a showed no selectivity, with a selectivity index of 1.12-1.40. Complex 2b was selective for the MCF-7 human tumor cell lines with IC of 59 ± 2 μM. This study demonstrates that the Cu(II) complexes 2a and 2b represent promising antitumoral compounds, and further studies are necessary to understand the molecular mechanisms of these effects.

摘要

两种基于 4-(芳基硫代/硒代)-1H-吡唑单齿双配体的新型 Cu(II)配合物(2a 和 2b)已被合成并通过红外光谱、高分辨率质谱(HRMS)和 X 射线晶体学进行了表征。为了为生物医学领域提出新的应用,我们评估了新合成配合物的抗氧化活性和细胞毒性。通过评估 Cu(II)配合物(2a-2b)抑制叠氮化钠诱导的活性物质(RS)形成的能力以及清除合成自由基 2,2-二苯基-1-苦基肼(DPPH)和 2,2-联氮双(3-乙基苯并噻唑啉-6-磺酸)(ABTS)的能力来评估其抗氧化活性。两种含硒(2a)和硫(2b)的铜配合物均表现出体外抗氧化活性。在低浓度下,化合物(1a-1b 和 2a-2b)对 V79 细胞没有细胞毒性。此外,还测试了游离配体(1a-1b)及其配合物(2a-2b)对两种人肿瘤细胞系:MCF-7(乳腺癌)和 HepG2(肝癌)的抗增殖活性。此外,还测试了 2a 对 U2OS(骨肉瘤)的作用。我们的结果表明,1a 和 1b 对人细胞系的生长抑制活性很小或没有。2a 化合物对人肿瘤细胞系表现出良好的细胞毒性活性。然而,2a 没有选择性,选择性指数为 1.12-1.40。配合物 2b 对 MCF-7 人肿瘤细胞系具有选择性,IC 为 59±2μM。这项研究表明,Cu(II)配合物 2a 和 2b 代表有前途的抗肿瘤化合物,需要进一步研究以了解这些作用的分子机制。

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