Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal-dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis.

硫代氨基咔唑（TSC）是铁螯合剂的一类，据信具有抗癌活性。三个TSC已经进入临床试验这一事实可以说明这种化合物类别的巨大应用潜力。螯合金属离子的能力导致细胞代谢和生长中的一些生化变化。决定TSC抗肿瘤活性的重要因素是铁调节蛋白的水平和每种癌细胞特有的抗氧化能力。然而，尽管人们对TSC的兴趣日益增加，但其抗癌活性的机制仍不清楚。对于更有效和合理的设计，确定和描述上述问题至关重要。在这份报告中，我们描述了在四个主要结构支架上设计的一系列新的TSC。评估了这些化合物对一系列癌细胞系（包括结肠癌，乳腺癌和神经胶质瘤）的抗癌活性。特别注意金属依赖性蛋白。还确定了测试的TSC对细胞周期和氧化还原稳态的影响。这些结果证实了不依赖p53的细胞凋亡机制。