Antitumor agents 222. Synthesis and anti-androgen activity of new diarylheptanoids.
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.
Ohtsu
Hironori
H
Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Itokawa
Hideji
H
Xiao
Zhiyan
Z
Su
Ching-Yuan
CY
Shih
Charles C-Y
CC
Chiang
Tzuying
T
Chang
Eugene
E
Lee
YiFen
Y
Chiu
Shang Yi
SY
Chang
Chawnshang
C
Lee
Kuo-Hsiung
KH
D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006536:Heptanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D006536:Heptanes