Anjomshoa Marzieh, Torkzadeh-Mahani Masoud, Dashtrazmi Ebrahim, Adeli-Sardou Mahboubeh
Department of Biotechnology, Institute of Science, High Technology & Environmental Science, Graduate University of Advanced Technology, Kerman, Iran.
Department of Nanochemistry, Institute of Science, High Technology & Environmental Science, Graduate University of Advanced Technology, Kerman, Iran.
J Fluoresc. 2016 Mar;26(2):545-58. doi: 10.1007/s10895-015-1739-2. Epub 2015 Dec 21.
The focus of the present work is the preparation of new metal-based nanodrug to overcome limitations of chemotherapy such as poor water solubility of most common chemotherapeutic drugs. The copper(II) complex of 1,2,4-triazine derivatives, Cu(dppt)2(H2O)2 (dppt is 5,6-diphenyl- 3- (2-pyridyl)-1,2,4-triazine), has been synthesized at nano-size by sonochemical method and characterized by FTIR, zetasizer, and scanning electron microscopy (SEM). The interaction of the complex and nanocomplex with fish sperm DNA (FS-DNA) and BSA have been investigated under physiological conditions by a series of experimental methods. The results have indicated that the complex binds to FS-DNA by two biding modes, viz., electrostatic and intercalates into the base pairs of DNA. The competitive study with ethidium bromide (EB) shows that the complex and nanocomplex competes for the DNA-binding sites with EB. Protein binding studies show that the complex and nanocomplex could bind with BSA. The results of synchronous fluorescence of BSA show that additions of the complex affect the microenvironment of both tyrosine and tryptophan residues during the binding process. The in vitro cytotoxicity of the complex (solution in DMSO) and nanocomplex (colloid in H2O) against the human carcinoma cell lines (MCF-7 and A-549) was evaluated by MTT assay. The results of in vitro cytotoxicity indicate that the complex and nanocomplex have excellent cytotoxicity activity against MCF-7 and A-549. Results of the microscopic analyses of the cancer cells confirm the results of the cytotoxicity.
本工作的重点是制备新型金属基纳米药物,以克服化疗的局限性,如大多数常见化疗药物水溶性差的问题。通过声化学方法合成了1,2,4-三嗪衍生物的铜(II)配合物Cu(dppt)2(H2O)2(dppt为5,6-二苯基-3-(2-吡啶基)-1,2,4-三嗪),并通过傅里叶变换红外光谱(FTIR)、zeta电位分析仪和扫描电子显微镜(SEM)对其进行了表征。在生理条件下,通过一系列实验方法研究了该配合物和纳米配合物与鱼精DNA(FS-DNA)和牛血清白蛋白(BSA)的相互作用。结果表明,该配合物通过静电和插入DNA碱基对两种结合模式与FS-DNA结合。与溴化乙锭(EB)的竞争研究表明,该配合物和纳米配合物与EB竞争DNA结合位点。蛋白质结合研究表明,该配合物和纳米配合物可以与BSA结合。BSA同步荧光结果表明,在结合过程中加入该配合物会影响酪氨酸和色氨酸残基的微环境。通过MTT法评估了该配合物(二甲基亚砜溶液)和纳米配合物(水溶液胶体)对人癌细胞系(MCF-7和A-549)的体外细胞毒性。体外细胞毒性结果表明,该配合物和纳米配合物对MCF-7和A-549具有优异的细胞毒性活性。癌细胞的显微镜分析结果证实了细胞毒性结果。