2. Academic Validation
  3. Design, synthesis and biological evaluation of novel thiosemicarbazone-indole derivatives targeting prostate cancer cells

Design, synthesis and biological evaluation of novel thiosemicarbazone-indole derivatives targeting prostate cancer cells

  • Eur J Med Chem. 2021 Jan 15:210:112970. doi: 10.1016/j.ejmech.2020.112970.
Zhang-Xu He 1,  Jin-Ling Huo 1,  Yun-Peng Gong 1,  Qi An 1,  Xin Zhang 1,  Hui Qiao 1,  Fei-Fei Yang 1,  Xin-Hui Zhang 1,  Le-Min Jiao 1,  Hong-Min Liu 2,  Li-Ying Ma 3,  Wen Zhao 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, 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, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
  • 3 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: maliying@zzu.edu.cn.
  • 4 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: zhaowen100@139.com.
PMID: 33153765 DOI: 10.1016/j.ejmech.2020.112970
Abstract

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.

Keywords

Apoptosis; Cell cycle; Proliferation; Prostate cancer; Thiosemicarbazone.

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