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含 Knoevenagel Schiff 碱缩合物的氧钒(IV)配合物作为潜在的化疗药物:合成、表征、生物筛选和抗增殖测定。

Oxovanadium(IV) complexes with Knoevenagel Schiff base condensate as impending chemotherapeutic agents: Synthesis, characterization, biological screening and anti-proliferative assay.

机构信息

Research Department of Chemistry, VHNSN College, Virudhunagar 626 001, India.

Research Department of Chemistry, VHNSN College, Virudhunagar 626 001, India.

出版信息

Bioorg Chem. 2017 Aug;73:100-108. doi: 10.1016/j.bioorg.2017.06.008. Epub 2017 Jun 19.

DOI:10.1016/j.bioorg.2017.06.008
PMID:28648922
Abstract

Two novel oxovanadium(IV) complexes [VOL1]SO(1) and [VOL2]SO(2) containing Knoevenagel condensate Schiff base ligand (L1/L2) have been synthesized and characterized by physical, spectral and analytical methods. These complexes are reported as ionic in nature on the basis of elemental composition and molar conductance, and possess square pyramidal geometry around the central metal ions. The binding interactions of (1) and (2) with calf thymus DNA (CT DNA) were explored by absorption spectrophotometric titration, cyclic voltammetry data and viscosity measurements. The calculated intrinsic binding constant values (K) for (1) and (2) obtained from UV-Vis absorption studies are 0.4×10 and 5.6×10 (M) respectively. These experimental results indicate that (1) and (2) are intercalative binders and avid binder to CT DNA with different affinities. These complexes exhibit significant oxidative cleavage of supercoiled plasmid (pUC18) DNA in the presence of activators. In particular, the in vitro antimicrobial efficacy of oxovanadium(IV) complexes reveal that they are more active than free ligands. Besides, the in vitro cytotoxic effect of the titled complexes were examined on a bundle of human tumor cell lines such as MCF-7 and HeLa cancerous cell lines by the MTT method. Interestingly, complex (2) exhibits more potent cytotoxic activity than the other complex and standard drug (cisplatin). The mode of cell death was assessed by Hoechst 33258 staining morphological studies.

摘要

两种新型的含 Knoevenagel 缩合希夫碱配体(L1/L2)的氧钒(IV)配合物[VOL1]SO(1)和[VOL2]SO(2)已通过物理、光谱和分析方法进行了合成和表征。这些配合物基于元素组成和摩尔电导率被报告为离子性质,并且在中心金属离子周围具有四方锥几何形状。通过吸收分光光度滴定、循环伏安法数据和粘度测量研究了(1)和(2)与小牛胸腺 DNA(CT DNA)的结合相互作用。从紫外可见吸收研究中获得的(1)和(2)的计算固有结合常数(K)值分别为 0.4×10 和 5.6×10(M)。这些实验结果表明,(1)和(2)是与 CT DNA 具有不同亲和力的嵌入结合剂和 avid 结合剂。这些配合物在有激活剂的情况下对超螺旋质粒(pUC18)DNA 表现出显著的氧化断裂。特别是,氧钒(IV)配合物的体外抗菌功效表明它们比游离配体更具活性。此外,通过 MTT 法在 MCF-7 和 HeLa 癌细胞系等一组人肿瘤细胞系上测试了标题配合物的体外细胞毒性作用。有趣的是,与其他配合物和标准药物(顺铂)相比,配合物(2)表现出更强的细胞毒性活性。通过 Hoechst 33258 染色形态学研究评估了细胞死亡的方式。

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