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9-氟-5-烷基-12(H)-喹诺[3,4-b][1,4]苯并噻嗪氯化物与DNA相互作用的初步光谱研究。

Preliminary spectroscopic studies of the interactions between 9-fluoro-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride and DNA.

作者信息

Owczarzy Aleksandra, Rogóż Wojciech, Kulig Karolina, Zięba Andrzej, Maciążek-Jurczyk Małgorzata

机构信息

Department of Physical Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055, Katowice, Poland.

Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055, Katowice, Poland.

出版信息

Biochem Biophys Rep. 2025 May 29;43:102067. doi: 10.1016/j.bbrep.2025.102067. eCollection 2025 Sep.

Abstract

Cancer treatment is one of the challenges of modern medicine. The advancement of new anticancer drugs requires a comprehensive understanding of their mechanism of action and structure-activity relationships. 9-fluoro-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride (Salt2) is a newly synthesized substance exhibiting promising anticancer activity. Deoxyribonucleic acid (DNA) is a macromolecule of high biological importance. DNA is essential for cellular development, including DNA replication, transcription and translation. Binding of small molecules to DNA can inhibit or modify cellular DNA function and induces cell death. In turn, it can allow to alleviate or control the disease. The objective of the research was to assess the interactions of a newly developed substance (Salt2) and calf thymus DNA (ctDNA) using UV-VIS, spectrofluorescence and circular dichroism spectroscopy. The UV-VIS and fluorescence analysis showed that Salt2 might form a strong, intercalative complex in the ground state with ctDNA. Due to the fact that Salt2 changes ctDNA structure it can be assumed, that Salt2 can effect on DNA replication, transcription and translation processes and inhibits or modifies cellular DNA function. The results obtained for the Salt2-ctDNA complex, not only encourage further research, but may also prove useful in determining binding to human cellular DNA.

摘要

癌症治疗是现代医学面临的挑战之一。新型抗癌药物的研发需要全面了解其作用机制和构效关系。9-氟-5-烷基-12(H)-喹诺[3,4-b][1,4]苯并噻嗪氯化物(盐2)是一种新合成的具有潜在抗癌活性的物质。脱氧核糖核酸(DNA)是一种具有高度生物学重要性的大分子。DNA对于细胞发育至关重要,包括DNA复制、转录和翻译。小分子与DNA结合可抑制或改变细胞DNA功能并诱导细胞死亡。进而,它可以缓解或控制疾病。本研究的目的是使用紫外可见光谱、荧光光谱和圆二色光谱评估新开发的物质(盐2)与小牛胸腺DNA(ctDNA)的相互作用。紫外可见光谱和荧光分析表明,盐2可能在基态与ctDNA形成强的嵌入复合物。由于盐2改变了ctDNA的结构,可以推测,盐2可影响DNA复制、转录和翻译过程,并抑制或改变细胞DNA功能。盐2-ctDNA复合物的研究结果不仅鼓励进一步研究,而且可能有助于确定其与人类细胞DNA的结合情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a3/12162055/dca5f444f952/gr1.jpg

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