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

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

Volume: 21 Issue: 17

Author(s): Xin Chen , Changqing Xu, Yuxia Li, Xiaoming Duan and Guisen Zhao*

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,China

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

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.

Cite this article as:

Chen Xin , Xu Changqing , Li Yuxia, Duan Xiaoming and Zhao Guisen*, Design, Synthesis and Biological Evaluation of 1-methyl-1H-pyrazole-5-Carboxamide Derivatives as Novel Anti-Prostate Cancer Agents, Anti-Cancer Agents in Medicinal Chemistry 2021; 21 (17) . https://dx.doi.org/10.2174/1871520621666210202162953