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新型含苯二酮配体的钯配合物氨基酸衍生物对人结肠癌细胞系的抗癌活性

Anticancer activity of novel amino acid derivative of palladium complex with phendione ligand against of human colon cancer cell line.

作者信息

Farhangian Hossein, Eslami Moghadam Mahboube, Divsalar Adeleh, Rahiminezhad Arezo

机构信息

Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran.

Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.

出版信息

J Biol Inorg Chem. 2017 Oct;22(7):1055-1064. doi: 10.1007/s00775-017-1483-y. Epub 2017 Aug 4.

DOI:10.1007/s00775-017-1483-y
PMID:28779308
Abstract

The aim of this work is the identification of the structural effect of amino acid-Pd complex on DNA as an intracellular target which was studied using various spectroscopic techniques such as fluorescence, UV-visible and circular dichroism in combination with a molecular docking study. Hence, a novel water-soluble palladium complex, [Pd(phendione)(isopentylglycine)]NO, has been synthesized and characterized by spectroscopic method. The anticancer activity of complex was investigated against human colon cancer cell line of HCT116 after 24 h of incubation using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, this complex was interacted with calf thymus DNA (ct-DNA) via positive cooperative interaction. The fluorescence data indicate that Pd complex is intercalated in DNA. These results were confirmed by circular dichroism spectra. The molecular docking results indicate that docking may be an appropriate method for the prediction and confirmation of experimental results. Complementary molecular docking results may be useful for the determination of the binding mechanism of DNA in pharmaceutical and biophysical studies providing new insight into the novel pharmacology and new solutions in the formulation of advanced oral drug delivery systems. Docking and spectroscopic studies show that new water-soluble Pd complex has anticancer activity and it can bind to DNA via intercalation and groove binding.

摘要

本研究旨在确定氨基酸 - 钯配合物对作为细胞内靶点的DNA的结构效应,为此采用了多种光谱技术,如荧光光谱、紫外可见光谱和圆二色光谱,并结合分子对接研究。因此,合成了一种新型水溶性钯配合物[Pd(苯二酮)(异戊基甘氨酸)]NO,并通过光谱方法对其进行了表征。使用MTT(3 - (4,5 - 二甲基噻唑 - 2 - 基) - 2,5 - 二苯基四氮唑溴盐)法,在孵育24小时后研究了该配合物对人结肠癌细胞系HCT116的抗癌活性。此外,该配合物通过正协同相互作用与小牛胸腺DNA(ct - DNA)相互作用。荧光数据表明钯配合物插入到了DNA中。圆二色光谱证实了这些结果。分子对接结果表明,对接可能是预测和确认实验结果的一种合适方法。互补的分子对接结果可能有助于确定药物和生物物理研究中DNA的结合机制,为新型药理学提供新的见解,并为先进口服药物递送系统的配方提供新的解决方案。对接和光谱研究表明,新型水溶性钯配合物具有抗癌活性,并且可以通过插入和沟槽结合与DNA结合。

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