Isoalkyl (isoalkyl = isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) derivatives of thiosalicylic acid (TSA) were prepared by alkylation of TSA with corresponding isoalkyl-chlorides in the alkaline water-ethanol solution. The new free copper(II)-complexes with corresponding S-isoalkyl derivatives of TSA (C1-copper(II)-complex with S-isopropyl derivative of thiosalicylic acid, C2-copper(II)-complex with S-isobutyl derivative of thiosalicylic acid and C3-copper(II)-complex with S-isoamyl derivative of thiosalicylic acid) have been synthesized by direct reaction of copper(II)-nitrate with ligand precursor and then characterized by microanalysis, infrared spectra (IR) and EPR (electron paramagnetic resonance) spectra. The spectroscopically predicted structure of the obtained binuclear copper(II)-complex with S-isopropyl derivative of thiosalicylic acid was confirmed by X-ray analysis. Single crystals suitable for X-ray measurements were obtained by slow crystallization from a water solution. Newly synthesized precursors S-isoalkyl derivatives of thiosalicylic acid and corresponding copper(II)-complexes moderately reduced viability of human and murine lung cancer cells, they showed similar cytotoxic effect on human colorectal cancer cells as cisplatin and lower cytotoxic effect than cisplatin toward normal fibroblasts, evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric technique. All new complexes exhibited apoptotic effect toward lung cancer cells, stronger than cisplatin, whereas only C3 induced significant apoptosis of colorectal cancer cells. Complex C1 showed significant antiproliferative effect against murine lung cancer cells, LLC1, while C2 reduced expression of Ki67 in human colorectal cancer cells. All tested complexes induced cell cycle arrest of HCT116 cells in G2/M phase.

中文翻译：

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双核铜（II）配合物与硫代水杨酸的某些S-异烷基衍生物的合成，表征和细胞毒活性。具有硫代水杨酸的S-异丙基衍生物的双核铜（II）配合物的晶体结构。

硫代水杨酸（TSA）的异烷基（异烷基=异丙基-（L1），异丁基-（L2）和异戊基-（L3））衍生物是通过将TSA与相应的异烷基氯化物在碱性水-乙醇溶液中烷基化而制备的。TSA的相应S-异烷基衍生物的新型游离铜（II）配合物（硫代水杨酸的S-异丙基衍生物的C1-铜（II）配合物，硫代水杨酸的S-异丁基衍生物的C2-铜（II）配合物通过硝酸铜（II）与配体前体的直接反应合成了丙烯酸和C3-铜（II）与硫代水杨酸的S-异戊基衍生物的配合物，然后通过微分析，红外光谱（IR）和EPR（电子顺磁共振）光谱。通过X射线分析证实了所获得的具有硫代水杨酸的S-异丙基衍生物的双核铜（II）配合物的光谱预测结构。通过从水溶液中缓慢结晶获得适用于X射线测量的单晶。新合成的硫代水杨酸前体S-异烷基衍生物和相应的铜（II）配合物适度降低了人和鼠肺癌细胞的活力，它们对人结肠直肠癌细胞的杀伤作用与顺铂相似，对正常成纤维细胞的杀伤力比顺铂低用MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑鎓）比色法评估。所有新的复合物均对肺癌细胞具有凋亡作用，比顺铂更强，而只有C3会诱导大肠癌细胞的显着凋亡。复合物C1对鼠类肺癌细胞LLC1表现出显着的抗增殖作用，而复合物C2降低人结肠直肠癌细胞中Ki67的表达。所有测试的复合物均诱导了G2 / M期HCT116细胞的细胞周期停滞。