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

被引：31

作者：

He, Zhang-Xu ^{[1
]}

Huo, Jin-Ling ^{[1
]}

Gong, Yun-Peng ^{[1
]}

An, Qi ^{[1
]}

Zhang, Xin ^{[1
]}

Qiao, Hui ^{[1
]}

Yang, Fei-Fei ^{[1
]}

Zhang, Xin-Hui ^{[1
]}

Jiao, Le-Min ^{[1
]}

Liu, Hong-Min ^{[1
]}

Ma, Li-Ying ^{[1
]}

Zhao, Wen ^{[1
]}

机构：

[1] Zhengzhou Univ, State Key Lab Esophageal Canc Prevent & Treatment, Key Lab Adv Pharmaceut Technol, Minist Educ China,Sch Pharmaceut Sci, Zhengzhou 450001, Henan, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 210卷

基金：

中国国家自然科学基金;

关键词：

Prostate cancer; Thiosemicarbazone; Proliferation; Cell cycle; Apoptosis; ANTITUMOR-ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ANTICANCER AGENTS; IRON CHELATORS; IN-VITRO; POTENT; INHIBITORS; PROLIFERATION; COMPLEXES; LIGANDS;

D O I：

10.1016/j.ejmech.2020.112970

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M, compared with normal WPMY-1 cells with the IC50 value of 19.470 mu M. 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. (C) 2020 Elsevier Masson SAS. All rights reserved.

引用

页数：20

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