Fernández-Delgado Elena, Estirado Samuel, Rodríguez Ana B, Luna-Giles Francisco, Viñuelas-Zahínos Emilio, Espino Javier, Pariente José Antonio
Neuroimmunophysiology and Chrononutrition Research Group, Department of Physiology, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain.
Coordination Chemistry Research Group, Department of Organic and Inorganic Chemistry, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain.
Pharmaceutics. 2023 Feb 18;15(2):696. doi: 10.3390/pharmaceutics15020696.
The synthesis of analogs of cisplatin, which is a widely used chemotherapeutic agent, using other metal centers could be an alternative for cancer treatment. Pd(II) could be a substitute for Pt(II) due to its coordination chemistry similarity. For that reason, six squared-planar Pd(II) complexes with thiazine and thiazoline ligands and formula [PdCl(L)] were synthesized and characterized in this work. The potential anticarcinogenic ability of the compounds was studied via cytotoxicity assay in three different human tumor cell lines, i.e., epithelial cervix carcinoma (HeLa), promyelocytic leukemia (HL-60), and histiocytic lymphoma (U-937). Data obtained showed that complexes with methyl substitutions did not modify cell viability, while no-methyl substituted compounds had a moderate cytotoxic effect on all three cell lines. The complexes with phenyl substitutions displayed the lowest IC values, which ranged between 46.39 ± 3.99 μM and 62.74 ± 6.45 μM. Moreover, Pd accumulation inside the cell was observed after incubation with any of the four complexes mentioned, and the two complexes with phenyl rings were found to induce an increase in the percentage of apoptotic cells. These results suggested that the presence of bulky substitutions on the ligands such as phenyl groups may influence the cytotoxicity of the chemotherapeutic agents synthesized.
使用其他金属中心合成广泛应用的化疗药物顺铂的类似物,可能是癌症治疗的一种替代方法。由于其配位化学相似性,钯(II)可以替代铂(II)。因此,本研究合成并表征了六种具有噻嗪和噻唑啉配体、化学式为[PdCl(L)]的平面正方形钯(II)配合物。通过在三种不同的人类肿瘤细胞系,即上皮宫颈癌(HeLa)、早幼粒细胞白血病(HL-60)和组织细胞淋巴瘤(U-937)中进行细胞毒性试验,研究了这些化合物的潜在抗癌能力。获得的数据表明,具有甲基取代的配合物不会改变细胞活力,而无甲基取代的化合物对所有三种细胞系都有中等程度的细胞毒性作用。具有苯基取代的配合物显示出最低的IC值,范围在46.39±3.99μM至62.74±6.45μM之间。此外,在用上述四种配合物中的任何一种孵育后,观察到细胞内有钯积累,并且发现具有苯环的两种配合物可诱导凋亡细胞百分比增加。这些结果表明,配体上存在如苯基等大体积取代基可能会影响所合成化疗药物的细胞毒性。