Certain metal complexes can have a great antitumor activity, as the use of cisplatin in therapy has been demonstrating for the past fifty years. Copper complexes, in particular, have attracted much attention as an example of anticancer compounds based on an endogenous metal. In this paper we present the synthesis and the activity of a series of copper(II) complexes with variously substituted salicylaldehyde thiosemicarbazone ligands. The in vitro activity of both ligands and copper complexes was assessed on a panel of cell lines (HCT-15, LoVo and LoVo oxaliplatin resistant colon carcinoma, A375 melanoma, BxPC3 and PSN1 pancreatic adenocarcinoma; BCPAP thyroid carcinoma, 2008 ovarian carcinoma, HEK293 non-transformed embryonic kidney), highlighting remarkable activity of the metal complexes, in some cases in the low nanomolar range. The copper(II) complexes 1–6 were also screened, with good results, against 3D spheroids of colon (HCT-15) and pancreatic (PSN1) cancer cells. Detailed investigations on the mechanism of action of the copper(II) complexes are also reported: they are able to potently inhibit Protein Disulfide Isomerase, a copper-binding protein, that is recently emerging as a new therapeutic target for cancer treatment. Good preliminary results obtained in C57BL mice indicate that this series of metal-based compounds could be a very promising weapon in the fight against cancer.

某些金属配合物可能具有很好的抗肿瘤活性，因为在过去的五十年中，顺铂在治疗中的应用已得到证明。作为基于内源金属的抗癌化合物的实例，特别是铜络合物引起了广泛的关注。在本文中，我们介绍了具有不同取代的水杨醛硫代半脲配体的一系列铜（II）配合物的合成和活性。在体外在一组细胞系（HCT-15，LoVo和LoVo奥沙利铂耐药结肠癌，A375黑色素瘤，BxPC3和PSN1胰腺腺癌，BCPAP甲状腺癌，2008年卵巢癌，HEK293非转化胚胎癌）中评估了配体和铜配合物的活性肾脏），突出了金属配合物的显着活性，在某些情况下在低纳摩尔范围内。铜（II）配合物1-6还针对结肠（HCT-15）和胰腺（PSN1）癌细胞的3D椭球体进行了筛选，并取得了良好的效果。还报道了有关铜（II）配合物作用机理的详细研究：它们能够有效抑制铜结合蛋白蛋白质二硫键异构酶，蛋白质二硫键异构酶最近已成为癌症治疗的新治疗靶标。在C57BL小鼠中获得的良好初步结果表明，这一系列基于金属的化合物可能是对抗癌症的非常有前途的武器。