Design, Synthesis and Biological Evaluation of Thiohydantoin Derivatives as Novel Anti-prostate Cancer Agents

Author(s):

Jianzhen Liu, Bo Liu, Yongkui Jing and Guisen Zhao   Pages 740 - 746 ( 7 )

Abstract:

A series of novel thiohydantoin derivatives were synthesized and evaluated for the abilities of inhibiting cell proliferation and prostate specific antigen (PSA) expression in prostate cancer cells. These derivatives selectively inhibited proliferation of AR positive LNCaP cells and PSA expression except compounds 5i and 5j. Compound 5t was approximately 15-fold more potent than MDV3100 to inhibit LNCaP cell proliferation. Compounds 5i and 5j inhibited cell growth of both AR positive LNCaP cells and AR negative PC-3 cells with potential to be developed as novel agents to treat antiandrogen resistant prostate cancer.

Keywords:

Thiohydantoin derivatives; androgen receptor; prostate cancer; antiandrogen; prostate specific antigen; anti-proliferation.

Affiliation:

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

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