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Synthesis and structure elucidation of novel salophen-based dioxo-uranium(VI) complexes: In-vitro and in-silico studies of their DNA/BSA-binding properties and anticancer activity
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2017-09-04 , DOI: 10.1016/j.ejmech.2017.08.068
S. Yousef Ebrahimipour , Maryam Mohamadi , Masoud Torkzadeh Mahani , Jim Simpson , Joel T. Mague , Iran Sheikhshoaei

The synthesis and characterization of three dioxo U(VI) complexes, [UO2(L1)(OH2)], [UO2(L2)DMF], and [UO2(L2)DMSO], [L1]2- = 1,1′-(4-methyl-1,2-phenylenebis (nitrilomethylidyne))di-2-naphtholate: [L2]2- = 1,1′-(o-phenylenebis (nitrilomethylidyne)) di-2-naphtholate, are reported. Elemental analysis, FT-IR, 1HNMR, UV–Vis spectroscopy, molar conductivity and single crystal X-ray diffraction were used to characterize the complexes. It was found that the complexes adopt a distorted pentagonal bipyramidal coordination geometry. The interaction of the synthesized complexes with DNA and bovine serum albumin was thoroughly investigated using both experimental and theoretical studies. UV–Vis absorption and fluorescence quenching techniques were applied to determine the binding parameters as well as the mechanism of the interaction of each complex with DNA and the protein. The results obtained suggested that interaction of the complexes with DNA occurred through partial intercalation into the minor grooves of DNA with binding constants in the range of 0.661 × 105–1.56 × 105 M−1. In addition, interaction of the complexes with bovine serum albumin quenched the fluorescence emission of the tryptophan residues of the protein binding constants and thermodynamic parameters were obtained from the fluorescence quenching experiments at different temperatures. The values of binding constants revealed moderate interactions between the synthesized complexes and the protein suggesting that this protein could act as a suitable vehicle for transportation of the compounds. The results of molecular docking confirmed those of the experimental studies. The anticancer properties of the title complexes were also evaluated through a study of the in vitro cytotoxicity of the compounds against the HT-29 and MCF-7 cancer cell lines and the DPSC normal cell line using an MTT assay.



中文翻译:

新型基于Salophen的二氧铀(VI)配合物的合成和结构阐明:DNA / BSA结合特性和抗癌活性的体外计算机模拟研究

三种二氧代U(VI)配合物[UO 2(L 1)(OH 2)],[UO 2(L 2)DMF]和[UO 2(L 2)DMSO],[L 1 ]的合成与表征] 2-  = 1,1'-(4-甲基-1,2-亚苯基二(亚硝基甲基二炔))二-2-萘甲酸:[L 2 ] 2-  = 1,1'-(苯基亚基(亚硝基甲基二炔))二报道了-2-萘甲酸酯。元素分析,FT-IR,1使用HNMR,UV-Vis光谱,摩尔电导率和单晶X射线衍射来表征配合物。发现该络合物采用扭曲的五边形双锥体配位几何形状。合成的复合物与DNA和牛血清白蛋白的相互作用已使用实验和理论研究进行了彻底研究。UV-Vis吸收和荧光猝灭技术用于确定结合参数以及每种复合物与DNA和蛋白质相互作用的机理。获得的结果表明,复合物与DNA的相互作用是通过部分插入DNA的小沟而发生的,结合常数在0.661×10 5 –1.56×10 5  M -1的范围内。。此外,配合物与牛血清白蛋白的相互作用使蛋白结合常数色氨酸残基的荧光发射猝灭,并且从不同温度下的荧光猝灭实验获得了热力学参数。结合常数的值揭示了合成的复合物和蛋白质之间的适度相互作用,这表明该蛋白质可以作为合适的载体运输化合物。分子对接的结果证实了实验研究的结果。还通过使用MTT测定法研究了化合物对HT-29和MCF-7癌细胞系和DPSC正常细胞系的体外细胞毒性研究来评估标题复合物的抗癌特性。

更新日期:2017-09-04
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