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手性-[三羰基(异烟酰基)铼(I)]配合物的非对映异构体拆分及其细胞毒性研究:针对神经胶质瘤作用机制的研究方法。

Diastereomeric Separation of Chiral -Tricarbonyl(iminopyridine) Rhenium(I) Complexes and Their Cytotoxicity Studies: Approach toward an Action Mechanism against Glioblastoma.

机构信息

Universidad Nacional Autónoma de México, Instituto de Química, Ciudad Universitaria, Ciudad de México 04510, México.

出版信息

J Med Chem. 2022 Jul 14;65(13):9281-9294. doi: 10.1021/acs.jmedchem.2c00561. Epub 2022 Jul 1.

Abstract

A series of new (tricarbonyl)rhenium(I) complexes were synthesized using chiral bidentate ligands (+)/(-)-iminopyridines (L/L). The reaction yielded a mixture of mononuclear Re(I) diastereoisomers, formulated as -[Br(CO)ReL]. Each single diastereoisomer was isolated and fully characterized. X-ray crystallography and circular dichroism spectra verified their enantiomeric nature. The cytotoxicity of each complex was evaluated against six cancer cell lines. The effect of the two complexes on viability, proliferation, and migration was analyzed on glioblastoma cell lines (U251 and LN229). Changes in the expression of histones, apoptotic, and key signaling proteins, as well as alterations in DNA structure, were also observed. These experiments showed that the chirality associated with both metal and ligand has a strong influence on cytotoxicity.

摘要

一系列新的(三羰基)铼(I)配合物使用手性双齿配体(+)/(-)-亚氨基吡啶(L/L)合成。该反应得到了单核 Re(I)非对映异构体的混合物,其化学式为-[Br(CO)ReL]。每个单一的非对映异构体都被分离并进行了充分的表征。X 射线晶体学和圆二色光谱证实了它们的对映体性质。评估了每个配合物对六种癌细胞系的细胞毒性。还分析了两种复合物对神经胶质瘤细胞系(U251 和 LN229)活力、增殖和迁移的影响。观察到组蛋白、凋亡和关键信号蛋白表达的变化,以及 DNA 结构的改变。这些实验表明,金属和配体的手性对细胞毒性有很大的影响。

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