Antitumor agents 222. Synthesis and anti-androgen activity of new diarylheptanoids.

Abstract

Fifteen new diarylheptanoids were synthesized and evaluated for antagonistic activity against androgen receptor (AR)-mediated reporter gene transcription using DU145, PC-3, and LNCaP prostate cancer cell lines. Most compounds showed activity in a 5alpha-dihydrotestosterone (DHT)-induced reporter gene expression assay in DU145 cells transfected with wild-type AR. Ten compounds (5, 8, 10, 14-15, and 18-22) were equipotent with hydroxyflutamide (HF), the anti-androgen currently available for the treatment of prostate cancer. However, except for compounds 5 and 10, none of the tested compounds was significantly effective in attenuating DHT-induced reporter gene expression in LNCaP cells, which contain endogenous mutant AR.

• Authors: Hironori Ohtsu, Hideji Itokawa, Zhiyan Xiao, Ching-Yuan Su, Charles C-Y Shih, Tzuying Chiang, Eugene Chang, YiFen Lee, Shang Yi Chiu, Chawnshang Chang, Kuo-Hsiung Lee
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 11 Issue 23 Pg. 5083-90 (Nov 17 2003) ISSN: 0968-0896 [Print] England
• PMID: 14604672 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Androgen Antagonists
• Antineoplastic Agents
• Heptanes

Topics

• Androgen Antagonists (chemical synthesis, pharmacology)
• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Heptanes (chemical synthesis, pharmacology)
• Humans
• Magnetic Resonance Spectroscopy
• Male
• Rats
• Spectrometry, Mass, Electrospray Ionization