1. Design, synthesis and biological evaluation of novel thiosemicarbazone-indole derivatives targeting prostate cancer cells.
- Author
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He, Zhang-Xu, Huo, Jin-Ling, Gong, Yun-Peng, An, Qi, Zhang, Xin, Qiao, Hui, Yang, Fei-Fei, Zhang, Xin-Hui, Jiao, Le-Min, Liu, Hong-Min, Ma, Li-Ying, and Zhao, Wen
- Subjects
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THIOSEMICARBAZONES , *CANCER cells , *BIOSYNTHESIS , *PROSTATE cancer , *LEAD compounds , *ANTINEOPLASTIC agents - 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 IC 50 value of 0.054 μM, compared with normal WPMY-1 cells with the IC 50 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. Image 1 • New thiosemicarbazone-indole derivatives were designed and synthesized based on previous work. • Most compounds were more sensitive to prostate cancer PC3 cells in comparison to other cancer cells. • 16f exhibited stronger activity and better safety profile than 3-AP, DPC and lead 4. • 16f induced G1/S cycle arrest and apoptosis in prostate cancer cells (PC3, DU-145) via ROS accumulation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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