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Design, Synthesis and Biological Evaluation of 1-methyl-1H-pyrazole-5-Carboxamide Derivatives as Novel Anti-Prostate Cancer Agents

[ Vol. 21 , Issue. 17 ]

Author(s):

Xin Chen , Changqing Xu, Yuxia Li, Xiaoming Duan and Guisen Zhao*   Pages 2368 - 2378 ( 11 )

Abstract:


Background: The Androgen Receptor (AR) signaling functionis a critical driving force for the progression of Prostate Cancer (PCa) to bring about anti-prostate cancer agents, and AR has been proved to be an effective therapeutic target even for Castration-Resistant Prostate Cancer (CRPC). Objective: In order to discover novel anti-prostate cancer agents, we performed structural modifications based on the lead compounds T3 and 10e.

Methods: A set of 1-methyl- 1H-pyrazole-5-carboxamide derivatives were synthesized and evaluated for their inhibitory activities against both expressions of Prostate-Specific Antigen (PSA) and growth of PCa cell lines.

Results: Compound H24 was found to be able to completely block PSA expression at 10μM, and showed prominent antiproliferative activity in both the LNCaP cell line (GI50 = 7.73μM) and PC-3 cell line (GI50 = 7.07μM).

Conclusion: These preliminary data supported a further evaluation of compound H24 as a potential agent to treat prostate cancer.

Keywords:

Androgen receptor, prostate cancer, pyrazole derivatives, prostate-specific antigen, antiproliferative activity, structural modification.

Affiliation:

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong



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