稀土-全反式维甲酸-精氨酸三元配合物的合成、表征及抗肿瘤活性研究

合成了4种新型稀土三元固体配合物:REL2L′Cl·nH2O(RE:Nd3+、Eu3+、La3+、Sc3+;L=全反式维甲酸;L′=L-精氨酸阳离子),并对其进行红外光谱、紫外光谱、荧光光谱、元素分析和TG-DTA等测试。利用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)测试方法,初步探讨了配合物对体外培养的人肝癌细胞HepG2、人肺癌细胞A549和人宫颈癌细胞Hela生长的影响。结果表明:4种稀土配合物和稀土硝酸盐、配体全反式维甲酸和L-精氨酸盐酸盐对3种癌细胞株的生长都有一定的抑制作用,但在一定的浓度范围内,三元固体配合物的抑制效果明显优于稀土硝酸盐和2种配体;稀土配合物对3种癌细胞株生长的抑制作用基本上随配合物浓度的增大而增强;在浓度为1 mmol·L-1时,4种配合物对3种肿瘤细胞的抑制率超过60%,ScL2L′Cl配合物表现出最强的作用,抑制率在80%以上。通过荧光,粘度和紫外光谱方法研究了配合物与药物靶分子DNA的相互作用,结果表明配合物与DNA以嵌入的方式相互作用,推测配合物抗肿瘤活性的起效与这种嵌入DNA双螺旋结构的作用方式有关

Study on Synthesis, Characterization and Antitumor Activity of Rare Earth Metal Complexes with All Trans Retinoic Acid and Arginine Acid

For the further research of drug applications of rare earth complexes, four complexes of RE L2 L'Cl·nH₂O (RE: Nd³⁺, Eu³⁺, La³⁺, Sc³⁺; L=all-trans retinoic acid; L'=L-arginine acid ion) were synthesized. The compositions of complexes were tested by IR, UV, fluorescence spectra, elemental analysis and TG-DTA methods. Meanwhile, the antitumor activity against HepG2, A549 and Hela in vitro growth cells was investigated by MTT test method, and the results showed that the synthesized four rare earth complexes have different degrees of inhibition on the growth of HepG2, A549 and Hela cells.And the inhibitory effect of complexes is significantly better than that of nitrate of rare earth and ligands. ScL2L'Cl complex is the best one with inhibition of the four under the concentration of 1 mmol·L^-1. The interaction of these complexes with DNA was studied by fluorescence spectra, viscosity and UV spectra, and the results showed that the type of interaction is mainly intercalation, which may be the one of reasons for antitumor activity of the complexes. The research provides certain ideas and experimental basis to design efficient and low toxicity of rare earth antitumor drugs.