Kostova Irena, Rastogi Vinod K, Kiefer Wolfgang, Kostovski Aleksandar
Department of Physics, CCS University, Meerut, India.
Arch Pharm (Weinheim). 2006 Nov;339(11):598-607. doi: 10.1002/ardp.200600077.
The complex of lanthanum (III) was synthesized reacting the respective inorganic salt with 5-aminoorotic acid in amounts equal to the metal:ligand molar ratio of 1:3. The complex was prepared by adding an aqueous solution of lanthanum (III) nitrate to an aqueous solution of the ligand, subsequently raising the pH of the mixture gradually to approx. 5.0 through addition of a dilute solution of sodium hydroxide. The structure of the final complex was determined by means of spectral data (IR, Raman,( 1)H-NMR) and elemental analysis. Significant differences in the IR spectrum of the complex were observed as compared to the spectrum of the ligand. A comparative analysis of the Raman spectrum of the complex with that of the free 5-aminoorotic acid allowed a straightforward assignment of the vibrations of the ligand groups involved in coordination. The ligand and the complex were tested for the cytotoxic activities on the chronic myeloid leukemia derived K-562, overexpressing the BCR-ABL fusion protein and the non-Hodgkin lymphoma derived DOHH-2, characterized by a re-expression of the anti-apoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentration-dependent matter, which enabled the construction of dose-response curves and the calculation of the corresponding IC(50 )values. The inorganic salt exerted a very weak cytotoxic effect on these cells, which is in contrast to the lanthanum (III) complex.
通过使相应的无机盐与5-氨基乳清酸以金属与配体的摩尔比为1:3的量反应,合成了镧(III)配合物。通过将硝酸镧(III)的水溶液加入到配体的水溶液中,随后通过加入氢氧化钠稀溶液将混合物的pH值逐渐提高到约5.0来制备该配合物。通过光谱数据(红外光谱、拉曼光谱、(1)H-核磁共振)和元素分析确定了最终配合物的结构。与配体的光谱相比,观察到配合物的红外光谱有显著差异。将配合物的拉曼光谱与游离5-氨基乳清酸的拉曼光谱进行对比分析,可以直接确定参与配位的配体基团的振动。测试了配体和配合物对慢性髓性白血病来源的K-562细胞系(过表达BCR-ABL融合蛋白)和非霍奇金淋巴瘤来源的DOHH-2细胞系(特征为抗凋亡蛋白bcl-2重新表达)的细胞毒性活性。所得结果表明,所测试的化合物以浓度依赖的方式对所评估的细胞系发挥了相当大的细胞毒性活性,这使得能够构建剂量反应曲线并计算相应的IC(50)值。无机盐对这些细胞的细胞毒性作用非常弱,这与镧(III)配合物形成对比。