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.
