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新型取代 2-(1H-苯并咪唑-2-基)喹啉的环金属铱(III)配合物的合成、表征、电化学和抗癌研究。

New cyclometalated iridium(III) complexes bearing substituted 2-(1H-benzimidazol-2-yl)quinoline: Synthesis, characterization, electrochemical and anticancer studies.

机构信息

Department of Engineering Basic Sciences, Faculty of Engineering and Natural Sciences, Istanbul Medeniyet University, Istanbul, Turkey.

Department of Biology, Faculty of Science, Pamukkale University, Denizli, Turkey.

出版信息

Bioorg Chem. 2024 Oct;151:107706. doi: 10.1016/j.bioorg.2024.107706. Epub 2024 Aug 8.

Abstract

New iridium(III) compounds (C-C) bearing 2-(1H-benzimidazol-2-yl)quinoline ligands with different side groups (benzyl, 2,3,4,5,6-pentamethylbenzyl and 2,3,4,5,6-pentafluorobenzyl) were synthesized and characterized by using spectroscopic analyses. The effects of different side groups of iridium compounds on the photophysical and electrochemical properties have been investigated. The cytotoxicity and apoptosis of the compounds have been evaluated on breast cancer cell lines using various methods including MTT assay, flow cytometry, qRT-PCR, and colony formation. The cytotoxicity of C, expressed as IC50 values, was found to be 11.76 μM for MDA-MB-231 and 5.35 μM for MCF-7 cells. For C, the IC50 value was 16.22 μM for MDA-MB-231 and 8.85 μM for MCF-7 cells. In both cell lines, increased levels of Bax and caspase 3, along with downregulation of BCL-2 and positive annexin V staining, were observed, confirming apoptosis. Moreover, the colony-forming abilities in both cell lines decreased after C and C complex treatment. All these results suggest that the compounds C and C may have potential in the treatment of breast cancer, though further research is needed to confirm their efficacy.

摘要

新的铱(III)化合物(C-C)带有不同侧基(苄基、2,3,4,5,6-五甲基苄基和 2,3,4,5,6-五氟苄基)的 2-(1H-苯并咪唑-2-基)喹啉配体已通过光谱分析进行了合成和表征。研究了铱化合物不同侧基对光物理和电化学性质的影响。通过 MTT 测定、流式细胞术、qRT-PCR 和集落形成等多种方法评价了化合物对乳腺癌细胞系的细胞毒性和细胞凋亡。化合物 C 的细胞毒性(表示为 IC50 值)对 MDA-MB-231 和 MCF-7 细胞分别为 11.76 μM 和 5.35 μM。对于 C,IC50 值对 MDA-MB-231 和 MCF-7 细胞分别为 16.22 μM 和 8.85 μM。在这两种细胞系中,均观察到 Bax 和 caspase 3 水平升高,BCL-2 下调以及阳性 annexin V 染色,证实了细胞凋亡。此外,经 C 和 C 配合物处理后,两种细胞系的集落形成能力均降低。所有这些结果表明,化合物 C 和 C 可能在乳腺癌的治疗中有一定潜力,但需要进一步研究来确认其疗效。

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