To discover novel anticancer agents with potent and low toxicity, we designed and synthesized a range of new thiosemicarbazone-indole analogues based on lead compound 4 we reported previously. Most compounds displayed moderate to high anticancer activities against five tested tumor cells (PC3, EC109, DU-145, MGC803, MCF-7). Specifically, the represented compound 16f possessed strong antiproliferative potency and high selectivity toward PC3 cells with the IC₅₀ value of 0.054 μM, compared with normal WPMY-1 cells with the IC₅₀ value of 19.470 μM. Preliminary mechanism research indicated that compound 16f could significantly suppress prostate cancer cells (PC3, DU-145) growth and colony formation in a dose-dependent manner. Besides, derivative 16f induced G1/S cycle arrest and apoptosis, which may be related to ROS accumulation due to the activation of MAPK signaling pathway. Furthermore, molecule 16f could effectively inhibit tumor growth through a xenograft model bearing PC3 cells and had no evident toxicity in vivo. Overall, based on the biological activity evaluation, analogue 16f can be viewed as a potential lead compound for further development of novel anti-prostate cancer drug.

为了发现具有强效和低毒性的新型抗癌药，我们基于先前报道的铅化合物4设计并合成了一系列新的硫代半碳酰胺-吲哚类似物。大多数化合物对五个测试的肿瘤细胞（PC3，EC109，DU-145，MGC803，MCF-7）显示出中度到高度的抗癌活性。具体地说，所表示的化合物16F具有强抗增殖效力和朝向PC3细胞与IC高选择性₅₀ 0.054μM的值，与正常WPMY-1细胞与IC相比₅₀ 19.470μM的值。初步机理研究表明，化合物16f可以剂量依赖性方式显着抑制前列腺癌细胞（PC3，DU-145）的生长和集落形成。此外，衍生物16f诱导G1 / S周期阻滞和凋亡，可能是由于MAPK信号通路的激活与ROS的积累有关。此外，分子16f可通过带有PC3细胞的异种移植模型有效抑制肿瘤生长，并且在体内没有明显的毒性。总体而言，基于生物学活性评估，类似物16f可被视为进一步开发新型抗前列腺癌药物的潜在先导化合物。