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基于苯并咪唑的、三联核中性环金属化和阳离子、NN-螯合的钌(ii)配合物的合成及抗增殖活性。

Synthesis and antiproliferative activity of benzimidazole-based, trinuclear neutral cyclometallated and cationic, NN-chelated ruthenium(ii) complexes.

机构信息

Department of Chemistry, University of Cape Town, Rondebosch 7701, Cape Town, South Africa.

出版信息

Dalton Trans. 2020 Jan 28;49(4):1143-1156. doi: 10.1039/c9dt03902c.

Abstract

A series of 2-phenyl and 2-pyridyl tris-benzimidazole ligands was reacted with the [Ru(p-cymene)Cl2]2 dimer to yield the corresponding neutral cyclometallated and cationic organoruthenium(ii) complexes. All of the synthesized compounds were characterized using an array of spectroscopic and analytical techniques, including 1H, 13C nuclear magnetic resonance (NMR), infrared spectroscopy and mass spectrometry. The trinuclear compounds were screened for their cytotoxicy against the MCF-7 breast cancer cell line and the triple negative MDA-MB-231 breast cancer cell line at concentrations of 10 and 20 μM. Overall, the 2-pyridyl ligands 10 and 11, and their corresponding trinuclear complexes [16][PF6]3 and [17][PF6]3, show the most promising activity as these compounds significantly reduce the percentage cell survival of MCF-7 and MDA-MB-231 breast cancer cell lines at the aforementioned fixed concentrations. It was observed that 10 and [16][PF6]3 show potency greater than that of cisplatin against the MCF-7 breast cancer cell line, and [17][PF6]3 shows potency comparable to that of cisplatin against the MCF-7 cell line. Additionally, the synthesized compounds were observed to have relatively low cytotoxicty towards MCF-12A breast epithelial cells and relatively higher selectivity towards MCF-7 breast cancer cells compared to cisplatin.

摘要

一系列 2-苯基和 2-吡啶基三苯并咪唑配体与[Ru(p-cymene)Cl2]2 二聚体反应,生成相应的中性环金属化和阳离子有机钌(ii)配合物。所有合成的化合物都使用一系列光谱和分析技术进行了表征,包括 1H、13C 核磁共振(NMR)、红外光谱和质谱。这些三核化合物在浓度为 10 和 20 μM 时,对 MCF-7 乳腺癌细胞系和三阴性 MDA-MB-231 乳腺癌细胞系的细胞毒性进行了筛选。总的来说,2-吡啶基配体 10 和 11,以及它们相应的三核配合物 [16][PF6]3 和 [17][PF6]3,表现出最有前途的活性,因为这些化合物在上述固定浓度下显著降低了 MCF-7 和 MDA-MB-231 乳腺癌细胞系的细胞存活率百分比。观察到 10 和 [16][PF6]3 对 MCF-7 乳腺癌细胞系的活性强于顺铂,而 [17][PF6]3 对 MCF-7 细胞系的活性与顺铂相当。此外,与顺铂相比,合成的化合物对 MCF-12A 乳腺上皮细胞的细胞毒性相对较低,对 MCF-7 乳腺癌细胞的选择性相对较高。

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