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增强与离子液体螯合的铑(III)配合物的生物活性:迈向靶向癌症治疗。

Enhancing Bioactivity of -Chelating Rhodium(III) Complexes with Ionic Liquids: Toward Targeted Cancer Therapy.

机构信息

University of Kragujevac, Faculty of Science, Radoja Domanovića 12, 34000 Kragujevac, Serbia.

University of Kragujevac, Institute for Information Technologies Kragujevac, Department of Science, Jovana Cvijića bb, 34000 Kragujevac, Serbia.

出版信息

J Med Chem. 2024 Aug 8;67(15):13349-13362. doi: 10.1021/acs.jmedchem.4c01220. Epub 2024 Jul 26.

Abstract

This study investigates the potential of using ionic liquids as cosolvents to enhance the solubility and activity of poorly soluble rhodium(III) complexes, particularly those with diene, pyridine derivatives, and camphor-derived bis-pyrazolylpyridine ligands, in relation to 5'-GMP, CT-DNA, and HSA as well as their biological activity. Findings indicate that ionic liquids significantly increase the substitution activity of these complexes toward 5'-GMP while only marginally affecting DNA/HSA binding affinities with molecular docking, further confirming the experimental results. Lipophilicity assessments indicated good lipophilicity. Notably, cytotoxicity studies show that is selectively effective against HeLa cancer cells, with IL1 and IL10 modulating the cytotoxic effects. Redox evaluations indicate that rhodium complexes induce oxidative stress in cancerous cells while maintaining redox balance in noncancerous cells. By elucidating the role of ionic liquids in modulating these effects, the study proposes a promising avenue for augmenting the efficacy and selectivity of cancer treatments, thus opening new horizons in cancer therapeutics.

摘要

本研究探讨了离子液体作为共溶剂的潜力,以提高在生理相关条件下,疏水性较差的铑(III)配合物的溶解度和活性,特别是那些具有二烯、吡啶衍生物和莰烯衍生的双吡唑基吡啶配体的配合物,以及它们与 5'-GMP、CT-DNA 和 HSA 的相互作用和生物活性。研究结果表明,离子液体显著提高了这些配合物对 5'-GMP 的取代活性,而分子对接仅对 DNA/HSA 结合亲和力产生微小影响,进一步证实了实验结果。亲脂性评估表明具有良好的亲脂性。值得注意的是,细胞毒性研究表明, 对 HeLa 癌细胞具有选择性作用,而 IL1 和 IL10 调节细胞毒性作用。氧化还原评估表明,铑配合物在诱导癌细胞氧化应激的同时,维持非癌细胞的氧化还原平衡。通过阐明离子液体在调节这些作用中的作用,本研究为提高癌症治疗的疗效和选择性提供了一个有前途的途径,从而为癌症治疗开辟了新的前景。

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