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水可溶性二氧代钒(V)配合物的芳酰腙:DNA/BSA 相互作用、疏水性和细胞选择性抗癌潜力。

Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential.

机构信息

Department of Chemistry, National Institute of Technology, Rourkela, 769008 Odisha, India.

Research Centre for Crystalline Materials, School of Medical and Life Sciences, 5 Jalan Universiti, Sunway University, Bandar Sunway 47500, Selangor Darul Ehsan, Malaysia.

出版信息

Inorg Chem. 2021 Oct 18;60(20):15291-15309. doi: 10.1021/acs.inorgchem.1c01899. Epub 2021 Oct 1.

Abstract

Five new anionic aqueous dioxidovanadium(V) complexes, [{VOL}A(HO)] (-), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (HL) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (HL) incorporating different alkali metals (A = Na, K, Cs) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of - were determined by time-dependent NMR and UV-vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of - confirmed the presence of vanadium(V) centers coordinated by two -oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of - was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, with an IC value of 5.42 ± 0.15 μM showed greater activity in comparison to cisplatin against the HT-29 cell line.

摘要

五种新型的阴离子水合二价钒(V)配合物,[{VOL}A(HO)] (-),配体为吡啶-4-羧酸(3-乙氧基-2-羟基苯亚甲基)腙(HL)和呋喃-2-羧酸(3-乙氧基-2-羟基苯亚甲基)腙(HL),其中包含不同的碱金属(A = Na,K,Cs)作为抗衡离子,通过各种物理化学技术合成并进行了表征。通过时间依赖性 NMR 和 UV-vis 确定了 - 的溶液相稳定性,还通过光谱技术获得了辛醇/水分配系数。 - 的 X 射线晶体学证实了钒(V)中心的存在,其由两个 - 氧-O 原子和二阴离子三齿配体的 O,N 和 O 原子配位。为了评估生物行为,通过光谱实验筛选了所有配合物与 DNA/蛋白质的结合倾向。最后,对 - 对结肠(HT-29)、乳腺(MCF-7)和宫颈(HeLa)癌细胞系和非癌细胞系 NIH-3T3 进行了细胞毒性研究。细胞毒性具有细胞选择性,对 HT-29 的活性比对其他细胞更高。此外,还解释了疏水性在细胞毒性中的作用,即最佳疏水性对于高细胞毒性是必不可少的。此外,伤口愈合试验的结果表明,在 HT-29 细胞中存在抗迁移作用。值得注意的是,与顺铂相比,[V(HL)(3-乙氧基-2-羟基苯亚甲基)吡啶-4-羧酸](5.42 ± 0.15 μM)在 HT-29 细胞系中表现出更高的活性。

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