Kostova I, Momekov G
Department of Chemistry, Faculty of Pharmacy, Medical University, 2 Dunav Street, Sofia 1000, Bulgaria.
Eur J Med Chem. 2006 Jun;41(6):717-26. doi: 10.1016/j.ejmech.2006.03.020. Epub 2006 May 12.
Complexes of zirconium (IV) with some bis-coumarin ligands have been synthesized. The zirconium (IV) complexes with bis-coumarins were characterized by different physicochemical methods-elemental analysis, IR-, and (1)H-NMR-spectroscopies and mass spectral data. The spectral data of zirconium (IV) complexes were interpreted on the basis of comparison with the spectra of the free ligands. The results of the ligands and their complexes, based on spectral data are informative and useful for suggestion of the metal-ligand binding mode. Cytotoxic screening by MTT assay was carried out. In the present study we performed comparative evaluation of the cytotoxic effects of the three newly synthesized zirconium complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia LAMA-84. The preliminary cytotoxicity screening program revealed that the investigated zirconium complexes induced 50% inhibition of the cell viability of HL-60 and LAMA-84 cells at micromolar concentrations and thus could be considered as biologically active. Independently of the tumor test system evaluated the complex of bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane proved superior to the remaining agents with respect to the IC(50) values obtained. The complexes of both the other coumarins evaluated proved to be less potent than the corresponding free ligands, as evidenced by the IC(50) values obtained. Thus the zirconium complexes with coumarin ligands represent a novel class of antiproliferative agents, which deserve further attention in search of anticancer lead compounds.
已合成了锆（IV）与一些双香豆素配体的配合物。通过不同的物理化学方法——元素分析、红外光谱、（1）H-核磁共振光谱和质谱数据对锆（IV）与双香豆素的配合物进行了表征。基于与游离配体光谱的比较对锆（IV）配合物的光谱数据进行了解释。基于光谱数据的配体及其配合物的结果对于推测金属-配体结合模式具有参考价值且很有用。通过MTT法进行了细胞毒性筛选。在本研究中，我们对三种新合成的锆配合物对急性髓性白血病来源的HL-60细胞和慢性髓性白血病LAMA-84细胞的细胞毒性作用进行了比较评估。初步的细胞毒性筛选程序表明，所研究的锆配合物在微摩尔浓度下可诱导HL-60和LAMA-84细胞的细胞活力抑制50%，因此可被视为具有生物活性。无论评估的肿瘤测试系统如何，双（4-羟基-2-氧代-2H-色烯-3-基）-（1H-吡唑-3-基）-甲烷配合物在所获得的IC（50）值方面被证明优于其余试剂。所评估的另外两种香豆素的配合物被证明比相应的游离配体效力更低，所获得的IC（50）值证明了这一点。因此，锆与香豆素配体的配合物代表了一类新型的抗增殖剂，在寻找抗癌先导化合物方面值得进一步关注。
