Ohtsu Hironori, Itokawa Hideji, Xiao Zhiyan, Su Ching-Yuan, Shih Charles C-Y, Chiang Tzuying, Chang Eugene, Lee YiFen, Chiu Shang Yi, Chang Chawnshang, Lee Kuo-Hsiung
Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Bioorg Med Chem. 2003 Nov 17;11(23):5083-90. doi: 10.1016/j.bmc.2003.08.029.
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.
合成了15种新的二芳基庚烷类化合物，并使用DU145、PC-3和LNCaP前列腺癌细胞系评估其对雄激素受体（AR）介导的报告基因转录的拮抗活性。在转染野生型AR的DU145细胞中进行的5α-二氢睾酮（DHT）诱导的报告基因表达试验中，大多数化合物表现出活性。10种化合物（5、8、10、14 - 15以及18 - 22）与目前可用于治疗前列腺癌的抗雄激素药物羟基氟他胺（HF）效力相当。然而，除化合物5和10外，在含有内源性突变AR的LNCaP细胞中，所测试的化合物均未显著有效地减弱DHT诱导的报告基因表达。
