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新型1,10-菲咯啉取代咪唑鎓盐的高效合成:探索其抗癌应用。

Efficient synthesis of novel 1,10 phenanthroline-substituted imidazolium salts: Exploring their anticancer applications.

作者信息

Çakır Sinem, Ilhan Süleyman, Atmaca Harika, Türkmen Hayati

机构信息

Department of Chemistry, Faculty of Science, Ege University, Bornova, 35100, Izmir, Turkey.

Department of Biology, Faculty of Engineering and Natural Sciences, Manisa Celal Bayar University, Manisa, Turkey.

出版信息

Eur J Med Chem. 2024 Nov 5;277:116775. doi: 10.1016/j.ejmech.2024.116775. Epub 2024 Aug 13.

DOI:10.1016/j.ejmech.2024.116775
PMID:39153333
Abstract

This study reports a new series of 1,10-phenanthroline-substituted imidazolium salts (1a-f), examining their design, synthesis, structure and anticancer activities. The structures of these salts (1a-f) were characterized using H, C NMR, elemental analysis, mass spectrometry and Fourier transform infrared (FT-IR) spectroscopies. The salts' cytotoxic activities were tested against cancer cell lines, specifically MCF-7, MDA-MB-231 and non-tumorigenic MCF-10A mammary cells. The study compared the impact of aliphatic and benzylic groups in the salts' structure on their anticancer activity. Screening results revealed that compound 1c, in particular, showed promising inhibitory activity against the growth of MDA-MB-231 breast cancer cells, with an IC value of 12.8 ± 1.2 μM, indicating its potential as a chemotherapeutic agent. Cell apoptosis analysis demonstrated a tendency for compound 1c to induce early apoptosis in breast cancer cells. The stability/aquation of compound 1c was investigated using H NMR spectroscopy and its binding modes with DNA were explored via UV-Vis spectroscopy. Additionally, the study investigated the interaction residues and docking scores of compound 1c and the reference drug doxorubicin against Bax and Bcl-2 proteins using molecular docking.

摘要

本研究报告了一系列新的1,10 - 菲咯啉取代的咪唑鎓盐(1a - f),并对其设计、合成、结构和抗癌活性进行了研究。这些盐(1a - f)的结构通过氢谱、碳谱、元素分析、质谱和傅里叶变换红外(FT - IR)光谱进行了表征。测试了这些盐对癌细胞系,特别是MCF - 7、MDA - MB - 231和非致瘤性MCF - 10A乳腺细胞的细胞毒性活性。该研究比较了盐结构中脂肪族和苄基对其抗癌活性的影响。筛选结果表明,化合物1c尤其对MDA - MB - 231乳腺癌细胞的生长表现出有前景的抑制活性,IC值为12.8 ± 1.2 μM,表明其作为化疗药物的潜力。细胞凋亡分析表明化合物1c有诱导乳腺癌细胞早期凋亡的趋势。使用氢谱研究了化合物1c的稳定性/水合作用,并通过紫外可见光谱探索了其与DNA的结合模式。此外,该研究还使用分子对接研究了化合物1c和参考药物阿霉素与Bax和Bcl - 2蛋白的相互作用残基和对接分数。

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