铂类化疗药物的众多副作用导致了设计以其他过渡金属代替铂的新疗法。在这里，我们研究了以前报道的含有S-异烷基衍生物、水杨酸和鸟嘌呤-5'-磷酸鸟苷（GMP）以及小牛胸腺DNA（CT-DNA）的铜(II)络合物与其抗肿瘤效应在结肠癌模型中的相互作用。所有三个铜(II)络合物都表现出与CT-DNA结合的亲和力，但没有显示出插入或脱离乙溴乙啶。分子对接研究揭示了这些络合物与B-形式DNA的小凹槽具有显著的亲和力，与DNA扩展相一致，并且对Z-形式DNA的亲和力更高，支持这样一个假设，即络合物与CT-DNA结合诱导了从B-形式到Z-形式DNA的局部转变。这些络合物在体外对结肠癌细胞表现出中等但选择性的细胞毒性效应。与硫化水杨酸的S-异戊基衍生物形成的铜(II)双核络合物展示出最高的细胞毒性效应，阻滞了肿瘤细胞在细胞周期的G2/M阶段，并且显著降低了原发异位小鼠结肠癌组织中炎性分子前白介素-1β、肿瘤坏死因子-α、细胞间粘附分子-1和血管细胞间粘附分子-1的表达，伴随着肿瘤生长和肺、肝转移的显著减少。

The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5'-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.