Novel thiosemicarbazone derivatives containing indole fragment as potent and selective anticancer agent

Eur J Med Chem. 2019 Dec 15:184:111764. doi: 10.1016/j.ejmech.2019.111764.

Zhangxu He ¹, Hui Qiao ¹, Feifei Yang ¹, Wenjuan Zhou ¹, Yunpeng Gong ¹, Xinhui Zhang ¹, Haojie Wang ¹, Bing Zhao ¹, Liying Ma ², Hong-Min Liu ³, Wen Zhao ⁴

Affiliations

1 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China.
2 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: maliying@zzu.edu.cn.
3 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
4 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: zhaowen100@139.com.

PMID: 31614257 DOI: 10.1016/j.ejmech.2019.111764

Abstract

Potent and safe Anticancer drugs research and development are still on the way to human health. In this report, a series of novel thiosemicarbazone derivatives containing indole fragment were designed and synthesized. Most compounds exhibited excellent antiproliferative activity against PC3, MGC803 and EC109 cell lines with low micromolar IC₅₀ (0.14-12μM). Especially, compound 5j can selectively inhibit PC3 cells in three tested tumor cells with IC₅₀ value of 0.14 μM, which may be attributed to a synergistic effect after introducing indole fragment into the TSC structure. Meanwhile, compound 5j displayed more selectivity in PC3 cells toward two normal WPMY-1 and GES-1 cell lines, compared to those of 3-AP and DPC. We also found that 5j can effectively inhibit PC3 cell proliferation, colonization and induce Apoptosis. What's more, 5j may significantly suppress migration and invasion by blocking the EMT process but had no effect on cell cycle. Collectively, our findings indicate that 5j with structure of thiosemicarbazone containing indole may serve as a useful Anticancer lead for further optimization and development.

Keywords

Apoptosis; Migration; Proliferation; Selectivity; Thiosemicarbazone.

Name
Email *

	Sorry, but the email address you supplied was invalid.