478
Z. Yao et al. / Bioorg. Med. Chem. Lett. 21 (2011) 475–478
7. Luthe, V.; Sugimoto, Y.; Puy, L.; Labrie, Y.; Solache, I. L.; Singh, M.; Labrie, F. J.
The hybrid 3, closely resembling structure features of finaste-
ride and epristeride, exhibited promising 5 -reductase inhibitory
effect in vitro. The aromatization of the A ring and the replacement
of the carboxylic group of the hybrid compound 3 led to dimin-
ished activities. This fully elaborated hybrid provides us a novel
template for the development of pharmacokinetically improved
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a
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13. Determination of 5a-reductase activity and its inhibition in the human prostate:
Human prostates were obtained surgically from patients with benign prostatic
hyperplasia and homogenized. The homogenate was incubated with 200 nM
[4-14C] testosterone and the test compound (in four different concentrations)
in the presence of 1 mM NADPH for 20 min at 37 °C. And the enzymatic
reaction was stopped by the addition of ethyl acetate and freezing. The control
experiments were performed without the test substances in every series. After
extraction the radioactive testosterone and dihydrotestosterone were
separated by TLC, a Packard Radiochromatogram Scanner was used to trace
the separated steroids. Following measurement of the radioactivity of the
analogues that can selectively bind to 5a-reductase, and may act
as potential therapeutic agents for the treatment of BPH.
Acknowledgments
We thank the Shanghai University Distinguished Professor
(Eastern scholars) Program (DF2009-02), and Pujiang Talent Plan
Project (09PJ1409200) for financial support.
dihydrotestosterone formed and the substrate testosterone, the 5a-reductase
activity was calculated and expressed in terms of pmol dihydrotestosterone
per mg of protein for a 20-min incubation. The inhibitory effects of the
compounds are given in terms of IC50 values.
References and notes
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