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含三齿芳酰腙和三苯基膦配体的镍(II)配合物的合成、DNA/牛血清白蛋白结合研究及生物学测定

Synthesis, DNA/BSA binding studies and biological assay of nickel(II) complexes incorporating tridentate aroylhydrazone and triphenylphosphine ligands.

作者信息

Li Yun, Li Yueqin, Wang Nana, Lin Dong, Liu Xiaohui, Yang Yong, Gao Qinwei

机构信息

College of Chemical Engineering, Jiangsu Key Lab for the Chemistry & Utilization of Agricultural and Forest Biomass, Nanjing Forestry University, Nanjing, China.

Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, China.

出版信息

J Biomol Struct Dyn. 2019 Nov 27;38(17):4977-4996. doi: 10.1080/07391102.2019.1694995.

Abstract

Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [HL = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and HL = '-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by antioxidant assays demonstrated high antioxidant activity against NO· and O˙ radicals. The anticancer activity of each complex was assessed through cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from HL ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC value equaled 9.7 μM, which showed potent cytotoxic activity over standard drug cisplatin.

摘要

制备了两种由三齿芳酰腙配体[HL = 2-羟基-3-甲氧基苯亚甲基)苯甲酰腙和HL = '-(2-羟基-3-甲氧基苯亚甲基)-2-羟基苯甲酰腙]和三苯基膦衍生的新型镍(II)三苯基膦配合物,并通过单晶X射线衍射分析确定了它们的分子结构。两种镍(II)配合物均显示出略微扭曲的平面正方形几何结构,其中一个三齿芳酰腙配体通过ONO供体原子配位,一个三苯基膦配体通过磷原子与镍中心配位。DNA相互作用研究表明,两种配合物对鲱鱼精DNA(HS-DNA)的亲和力均高于相应的游离芳酰腙配体。分子对接研究表明,两种配合物均可通过双螺旋中相邻碱基对之间的苯环插入与DNA结合。同时,牛血清白蛋白(BSA)结合研究表明,配合物可与BSA有效相互作用并改变BSA的二级结构。通过抗氧化试验对合成配合物进行的进一步药理学评估显示,其对NO·和O˙自由基具有高抗氧化活性。通过对A549和MCF-7癌细胞以及正常L-02细胞系的细胞毒性试验(CCK-8试剂盒)评估了每种配合物的抗癌活性。值得注意的是,发现由HL配体衍生的Ni(II)配合物对MCF-7癌细胞具有更强的细胞毒性,IC值为9.7μM,显示出比标准药物顺铂更强的细胞毒性活性。

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