Matesanz A I, Pérez J M, Navarro P, Moreno J M, Colacio E, Souza P
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
J Inorg Biochem. 1999 Jul 30;76(1):29-37. doi: 10.1016/s0162-0134(99)00105-1.
The preparation of palladium(II) complexes of 3,5-diacyl-1,2,4-triazole bis(thiosemicarbazone) (H2L2), 2,6-diacylpyridine bis(thiosemicarbazone) (H2L3) and benzyl bis(thiosemicarbazone) (H2L4) is described. The new complexes [PdCl2(H2L2)] (1), [PdCl2(H2L3)] (2) and [PdL4].DMF (3) have been characterized by elemental analyses and spectroscopic studies (IR, 1H NMR and UV-Vis). The crystal and molecular structure of PdL4.DMF (L = bideprotonated form of benzyl bis(thiosemicarbazone)) has been determined by single-crystal X-ray diffraction: green triclinic crystal, a = 10.258(5), b = 10.595(5), c = 11.189(5) A, alpha = 97.820(5), beta = 108.140(5), gamma = 105.283(5) degrees, space group P1, Z = 1. The palladium atom is tetracoordinated by four donor atoms (SNNS) from L4 to form a planar tricyclic ligating system. The testing of the cytotoxic activity of compound 3 against several human, monkey and murine cell lines sensitive (HeLa, Vero and Pam 212) and resistant to cis-DDP (Pam-ras) suggests that compound 3 might be endowed with important antitumor properties since it shows IC50 values in a microM range similar to those of cis-DDP [cis-diamminedichloroplatinum(II)]. Moreover, compound 3 displays notable cytotoxic activity in Pam-ras cells resistant to cis-DDP (IC50 values of 78 microM versus 156 microM, respectively). On the other hand, the analysis of the interaction of this novel Pd-thiosemicarbazone compound with DNA secondary structure by means of circular dichroism spectroscopy indicates that it induces on the double helix conformational changes different from those induced by cis-DDP.
本文描述了3,5 - 二酰基 - 1,2,4 - 三唑双（硫代氨基脲）（H₂L₂）、2,6 - 二酰基吡啶双（硫代氨基脲）（H₂L₃）和苄基双（硫代氨基脲）（H₂L₄）的钯（II）配合物的制备。新配合物[PdCl₂(H₂L₂)]（1）、[PdCl₂(H₂L₃)]（2）和[PdL₄]·DMF（3）已通过元素分析和光谱研究（红外光谱、¹H核磁共振光谱和紫外 - 可见光谱）进行了表征。通过单晶X射线衍射确定了PdL₄·DMF（L = 苄基双（硫代氨基脲）的双去质子化形式）的晶体和分子结构：绿色三斜晶体，a = 10.258(5)，b = 10.595(5)，c = 11.189(5) Å，α = 97.820(5)，β = 108.140(5)，γ = 105.283(5)°，空间群P1，Z = 1。钯原子由来自L₄的四个供体原子（SNNS）进行四配位，形成一个平面三环配位体系。对化合物3针对几种对顺铂敏感（HeLa、Vero和Pam 212）以及对顺铂耐药（Pam - ras）的人、猴和鼠细胞系的细胞毒性活性测试表明，化合物3可能具有重要的抗肿瘤特性，因为其IC₅₀值在微摩尔范围内，与顺 - 二氯二氨合铂（II）[顺铂]相似。此外，化合物3在对顺铂耐药的Pam - ras细胞中显示出显著的细胞毒性活性（IC₅₀值分别为78微摩尔和156微摩尔）。另一方面，通过圆二色光谱法分析这种新型钯 - 硫代氨基脲化合物与DNA二级结构的相互作用表明，它在双螺旋上诱导的构象变化与顺铂诱导的不同。
