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第二种金属对配合物[Ru(η-C₆H₆)(Cl₂)(dmoPTA)]的抗增殖性能的显著影响

The Significant Influence of a Second Metal on the Antiproliferative Properties of the Complex [Ru(η -C H )(Cl )(dmoPTA)].

作者信息

Kordestani Nazanin, Abas Elisa, Grasa Laura, Alguacil Andres, Scalambra Franco, Romerosa Antonio

机构信息

Área de Química Inorgánica-CIESOL Facultad de Ciencias, Universidad de Almería, Carr. Sacramento, s/n, 04120, La Cañada, Almería, Spain.

Departamento de Farmacología, Fisiología y Medicina Legal y Forense Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain.

出版信息

Chemistry. 2022 Jan 13;28(3):e202103048. doi: 10.1002/chem.202103048. Epub 2021 Dec 8.

Abstract

Complexes [Ru(η -C H )(Cl )(HdmoPTA)](OSO CF ) (1), [Ru(η -C H )(Cl )(dmoPTA)] (2) and [Ru(η -C H )(Cl )-μ-dmoPTA-1κP:2κ N,N'-MCl ] (M=Zn (3), Co (4), Ni (5), dmoPTA=3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) have been synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structures of 1, 3 and 5 were obtained by single-crystal X-ray diffraction. The antiproliferative activity of the complexes was evaluated against colon cancer cell line Caco-2/TC7 by using the MTT protocol. The monometallic ruthenium complexes 1 and 2 were found to be inactive, but the bimetallic complexes 3, 4 and 5 display an increased activity (IC 3: 9.07±0.27, 4: 5.40±0.19, 5: 7.15±0.30 μM) compared to cisplatin (IC =45.6±8.08 μM). Importantly, no reduction in normal cell viability was observed in the presence of the complexes. Experiments targeted to obtain information on the possible action mechanism of the complexes, such as cell cycle, ROS and gene expression studies, were performed. The results showed that the complexes display different properties and action mechanism depending on the nature of metal, M, bonded to the CH N atoms.

摘要

已合成了配合物Ru(η⁵-C₅H₅)(Cl)₂(HdmoPTA) (1)、[Ru(η⁵-C₅H₅)(Cl)₂(dmoPTA)] (2) 和[Ru(η⁵-C₅H₅)(Cl)₂-μ-dmoPTA-1κP:2κN,N'-MCl₂] (M = Zn (3)、Co (4)、Ni (5),dmoPTA = 3,7-二甲基-1,3,7-三氮杂-5-磷杂双环[3.3.1]壬烷),并通过元素分析和光谱技术对其进行了表征。通过单晶X射线衍射获得了1、3和5的晶体结构。使用MTT法评估了这些配合物对结肠癌细胞系Caco-2/TC7的抗增殖活性。发现单金属钌配合物1和2无活性,但双金属配合物3、4和5显示出增强的活性(IC₅₀:3为9.07±0.27、4为5.40±0.19、5为7.15±0.30 μM),相比之下顺铂的IC₅₀ = 45.6±8.08 μM。重要的是,在存在这些配合物的情况下未观察到正常细胞活力的降低。进行了旨在获取有关配合物可能作用机制信息的实验,如细胞周期、活性氧和基因表达研究。结果表明,根据与CH₃N原子键合的金属M的性质,这些配合物表现出不同的性质和作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bc/9299940/389fa31f5bc3/CHEM-28-0-g010.jpg

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