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潜在的用于选择性损伤线粒体或溶酶体的抗癌剂:萘酰亚胺修饰的荧光生物标志物半夹心铱(III)和钌(II)配合物。

Potential anticancer agent for selective damage to mitochondria or lysosomes: Naphthalimide-modified fluorescent biomarker half-sandwich iridium (III) and ruthenium (II) complexes.

机构信息

Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, China.

Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, China.

出版信息

Eur J Med Chem. 2019 Nov 1;181:111599. doi: 10.1016/j.ejmech.2019.111599. Epub 2019 Aug 6.

DOI:10.1016/j.ejmech.2019.111599
PMID:31408807
Abstract

In this work, five naphthalimide-modified half-sandwich iridium and ruthenium complexes ([(η-Cp)Ir(NˆN)Cl]PF, [(η-p-cym)Ru(NˆN)Cl]PF) have been presented. The anticancer activities of the complexes against various cancer cell lines were investigated, among them, complexes 2 and 4 showed better anticancer activity than cisplatin, and their anticancer activity is better than complex 5 without fluorophore. In addition, a series of biological tests of complex 2 were performed using flow cytometry, the results indicated that the complex could induce cell death in a variety of ways. By changing of the ligands, the complexes exhibited different photophysical properties, and the mechanism of action of the complexes entering the cell and inducing apoptosis are different. Moreover, complex 2 successfully targeted mitochondria, while complex 4 targeted lysosomes, causing mitochondrial damage and lysosomal damage to induce apoptosis. Excitingly, complex 2 has good antimetastatic ability to cancer cells. Furthermore, complexes 2 and 4 did not have a significant effect on the NADH binding reaction, but they had a moderate binding ability to BSA.

摘要

在这项工作中,我们提出了五个萘酰亚胺修饰的半夹心铱和钌配合物([(η-Cp)Ir(NˆN)Cl]PF、[(η-p-cym)Ru(NˆN)Cl]PF)。研究了这些配合物对各种癌细胞系的抗癌活性,其中配合物 2 和 4 的抗癌活性优于顺铂,且其抗癌活性优于没有荧光团的配合物 5。此外,通过流式细胞术对配合物 2 进行了一系列生物学测试,结果表明该配合物可以通过多种方式诱导细胞死亡。通过改变配体,配合物表现出不同的光物理性质,并且配合物进入细胞并诱导细胞凋亡的作用机制也不同。此外,配合物 2 成功靶向线粒体,而配合物 4 靶向溶酶体,导致线粒体损伤和溶酶体损伤,从而诱导细胞凋亡。令人兴奋的是,配合物 2 对癌细胞具有良好的抗转移能力。此外,配合物 2 和 4 对 NADH 结合反应没有显著影响,但它们对 BSA 具有适度的结合能力。

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