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几种含有N-(2-羟乙基)-N'-苯甲酰基硫脲和1,10-菲咯啉配体的金属配合物的DNA结合、DNA切割及与人血清白蛋白的相互作用

DNA binding, DNA cleavage and HSA interaction of several metal complexes containing N-(2-hydroxyethyl)-N'-benzoylthiourea and 1,10-phenanthroline ligands.

作者信息

Peng Bo, Gao Zhuantao, Li Xibo, Li Tingting, Chen Guorong, Zhou Min, Zhang Ji

机构信息

Key Laboratory of Bioelectrochemistry and Environmental Analysis of Gansu Province, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, 730070, China.

College of Life Science, Northwest Normal University, Lanzhou, 730070, China.

出版信息

J Biol Inorg Chem. 2016 Oct;21(7):903-16. doi: 10.1007/s00775-016-1388-1. Epub 2016 Aug 29.

Abstract

Four novel ternary metal complexes of the type [M(Phen)(L1)2)] [phen = 1,10-phenanthroline, L1 = N-(2-hydroxyethyl)-N'-benzoylthiourea, M = Ni(II)(1), Co(II) (2), Cu(II) (3), Pd(II) (4)] were synthesized. The organic ligands and their corresponding organometallic complexes have been characterized using UV-vis absorption spectroscopy, element analysis, infrared radiation spectroscopy and fluorescence spectra. DNA binding and cleavage studies of these complexes were conducted in detail. In vitro DNA-binding properties were studied by electronic absorption spectra and fluorescence spectra methods. The results indicate that all of the ternary metal complexes can efficiently bind to DNA via intercalation mode. The DNA-binding constants for all ternary compounds are around 4 × 10(6) M(-1). The binding propensity of the complexes to human serum albumin (HSA) was also investigated. Agarose gel electrophoresis study revealed that the metal complexes could cleave super-coiled pBR322 DNA to a nicked form in the absence of external agents. In vitro anti bacterial studies show that copper complex has weak antibacterial activities. Copper complex exhibits a better biological activity among all complexes. This study provides a new perspective and evaluation on the role and importance of the effect factors on the medicinal properties of benzoylthiourea compounds. Synchronous fluorescence spectra of HSA (10 μM) as a function of concentration of the complexes 1-4.

摘要

合成了四种新型的[M(Phen)(L1)₂]类型的三元金属配合物(其中phen = 1,10 - 菲咯啉,L1 = N - (2 - 羟乙基)-N'-苯甲酰基硫脲,M = Ni(II)(1)、Co(II)(2)、Cu(II)(3)、Pd(II)(4))。利用紫外可见吸收光谱、元素分析、红外光谱和荧光光谱对有机配体及其相应的有机金属配合物进行了表征。详细研究了这些配合物与DNA的结合和切割情况。通过电子吸收光谱和荧光光谱法研究了其体外DNA结合特性。结果表明,所有三元金属配合物均能通过嵌入模式有效地与DNA结合。所有三元化合物的DNA结合常数约为4×10⁶ M⁻¹。还研究了配合物与人血清白蛋白(HSA)的结合倾向。琼脂糖凝胶电泳研究表明,在没有外部试剂的情况下,金属配合物可将超螺旋pBR322 DNA切割成切口形式。体外抗菌研究表明,铜配合物具有较弱的抗菌活性。在所有配合物中,铜配合物表现出较好的生物活性。本研究为苯甲酰基硫脲化合物药用特性的影响因素的作用和重要性提供了新的视角和评估。HSA(10 μM)的同步荧光光谱随配合物1 - 4浓度的变化。

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