铜、铁、锌-氟尿嘧啶配合物合成及其对肿瘤细胞增殖的抑制  

Copper, iron, zinc-fluorouracil complexes synthesized in vitro inhibit tumor cell proliferation

作　　者：周轶平[1] 陈元晓[2] 周云[3] 石中正 罗敏[1] 钟文远[5] 陈英杰[4] 

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南省昆明市650500 [2]昆明医科大学生物学教研室,云南省昆明市650500 [3]云南省广播电视大学化学系,云南省昆明市650000 [4]昆明医科大学解剖学教研室,云南省昆明市650500 [5]昆明学院化学系,云南省昆明市650031

出　　处：《中国组织工程研究》2014年第39期6309-6315,共7页Chinese Journal of Tissue Engineering Research

基　　金：云南省应用基础研究计划项目(2011FZ098);云南省天然药物药理重点实验室开放基金(20130G11;2013G012);云南省教育厅科学研究基金(2012Y010;2014Z060);国家自然科学基金(31101616;31160425)~~

摘　　要：背景:有机抗癌药与金属盐形成配合物后会形成新的结构或改变离子浓度,因此改变二者的毒性与活性而产生协同作用。目的:寻求高效低毒的新型金属-氟尿嘧啶配合物抗肿瘤药物。方法:以铜、铁、锌盐和氟尿嘧啶为原料,合成了4种配合物,分别为[Cu(5-Fu)2Cl2],[Cu(5-Fu)2(NO3)2],[Fe(5-Fu)3]SO4和[Zn(5-Fu)2Cl2]。用元素分析和质谱法分析配合物的化学结构。分别以4种配合物溶液、4种盐溶液、顺铂、氟尿嘧啶培养人白血病细胞株K562与人结肠癌细胞株HCT-116,改良MTT法测试细胞增殖。结果与结论:配合物的元素分析及摩尔电导数据初步确定了配合物的化学式,质谱结果进一步证明氟尿嘧啶确实与金属离子Cu2+、Fe2+、Zn2+配位。在0.1-100 mg/L质量浓度范围内,4种配合物对K562和HCT-116细胞增殖均有不同程度的抑制作用,4种配合物对K562和HCT-116细胞增殖的IC50值均低于氟尿嘧啶组,其细胞毒活性是氟尿嘧啶的1.5-7.8倍。表明铜盐、锌盐、铁盐与氟尿嘧啶形成配合物后有协同抑制肿瘤组织细胞增殖的作用。BACKGROUND：Anticancer drug and organic metal complexes wil form a new structure or a change in ion concentration, thus changing both the activity and toxicity to produce a synergistic effect. OBJECTIVE：To synthesize new high-efficient and low-toxic metal-fluorouracil complexes as anticancer drugs. METHODS：Copper, zinc and iron salts and fluorouracil were used to synthesize four copper, zinc and iron-fluorouracil complexes that were [Cu（5-Fu）2Cl2], [Cu（5-Fu）2（NO3）2], [Fe（5-Fu）3]SO4 and [Zn（5-Fu）2Cl2]. Preliminary chemical structures of the four complexes were confirmed by elemental analysis and mass spectrometry. Their inhibitory activity on human cancer cells, human leukemia cellline K562 and human colon cancer cellline HCT-116, was measured by MTT colorimetric assay. RESULTS AND CONCLUSION：[Cu（5-Fu）2Cl2], [Cu（5-Fu）2（NO3）2], [Zn（5-Fu）2Cl2] and [Fe（5-Fu）3SO4] were successful y synthesized. These four complexes at a mass concentration of 0.1-100 mg/L inhibited the＆amp;nbsp;proliferation of K562 and HCT-116 to different extents. The IC 50 values of these four complexes on K562 and HCT-116 cells were lower than those of fluorouracil, and their cytotoxicity was 1.5-7.8 times higher than that of fluorouracil. To conclude, copper/iron/zinc-fluorouracil complexes exhibit synergic inhibitory effects on cancer cellproliferation.

关 键 词：生物材料 材料相容性 铜 铁 锌-氟尿嘧啶配合物 合成 肿瘤细胞 增殖抑制 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]