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以酰基丙酮酸为配体的铜(II)配合物的合成、表征、抗肿瘤潜力及作用机制研究:与生物分子的相互作用及动力学研究

Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study.

作者信息

Joksimović Nenad, Petronijević Jelena, Radisavljević Snežana, Petrović Biljana, Mihajlović Kristina, Janković Nenad, Milović Emilija, Milivojević Dušan, Ilić Bojana, Djurić Ana

机构信息

University of Kragujevac, Faculty of Science, Department of Chemistry Radoja Domanovića 12 34000 Kragujevac Serbia

University of Kragujevac, Institute for Information Technologies Kragujevac, Department of Sciences Jovana Cvijića bb 34000 Kragujevac Serbia.

出版信息

RSC Adv. 2022 Oct 26;12(47):30501-30513. doi: 10.1039/d2ra05797b. eCollection 2022 Oct 24.

Abstract

Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5'-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice.

摘要

考虑到找到治疗肿瘤等恶性疾病的方法的紧迫性,我们合成并表征了一小系列与生物重要配体(如酰基丙酮酸)形成的新型铜(II)配合物。除此之外,我们还使用了另外四种与相同类型配体形成的铜(II)配合物来研究其抗肿瘤潜力。使用MTT法在三种肿瘤细胞系和一种正常人细胞系上检测了铜(II)配合物的抗肿瘤潜力。所有七种测试配合物均显示出非常好的细胞毒性作用。选择了两种显示出最佳抗肿瘤潜力的铜配合物进行进一步测试,这些测试表明它们在未来具有最佳的潜在应用潜力。使用细胞周期、ROS水平、氧化性DNA损伤以及与缺氧分析相关的蛋白质等测试详细研究了这些配合物的活性机制。此外,我们还研究了这些配合物与生物分子(郭、肌苷、5'-鸟苷酸、牛血清白蛋白和DNA)的结合能力。结果表明,测试化合物通过嵌入作用与DNA分子强烈结合。此外,还表明测试化合物能充分结合牛血清白蛋白分子,这表明这些化合物在未来临床实践中的某些应用具有更大的潜力

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9422/9597287/bbac89f3f86e/d2ra05797b-f1.jpg

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