Wu Jun, Guo Yafei, Chen Jun, Hu Sangsang, Sun Ke, Hu Hongyu, Fang Meijuan, Xue Yuhua
Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, China, 361102.
Xingzhi College, Zhejiang Normal University, Jinhua, Lanxi, 321004, China.
Chem Biodivers. 2021 Dec;18(12):e2100671. doi: 10.1002/cbdv.202100671. Epub 2021 Nov 5.
To discover new anticancer agents, two series of thiosemicarboxamide derivatives were synthesized and evaluated for their antiproliferative activity against human cancer cells in vitro. Most target compounds (especially 3f, 3g, and 3h) exhibit potent antiproliferative activity against HeLa cells. Importantly, compound 3h, bearing a 4-methylphenyl substituent at N position of thiourea moiety, has significant and broad-spectrum inhibitory activities against cancer cells (HepG2, HeLa, MDA-MB231, A875, and H460 cells) with low IC values (<5.0 μM) and shows low toxicity to normal LO2 and MRC-5 cells. Further studies show that compound 3h exerts high inhibitory activity in cancer cells by inducing the G2/M-phase arrest of cancer cells. Collectively, this study presents compound 3h as a new entity for the development of cell cycle arrest inducers for the treatment of cancer.
为了发现新的抗癌药物，合成了两个系列的硫代半羧酰胺衍生物，并对其体外抗人癌细胞增殖活性进行了评估。大多数目标化合物（尤其是3f、3g和3h）对HeLa细胞表现出强大的抗增殖活性。重要的是，在硫脲部分的N位带有4-甲基苯基取代基的化合物3h，对癌细胞（HepG2、HeLa、MDA-MB231、A875和H460细胞）具有显著且广谱的抑制活性，IC值较低（<5.0 μM），并且对正常的LO2和MRC-5细胞显示出低毒性。进一步研究表明，化合物3h通过诱导癌细胞的G2/M期阻滞在癌细胞中发挥高抑制活性。总的来说，本研究将化合物3h作为一种用于开发细胞周期阻滞诱导剂以治疗癌症的新实体。
