Molecular Interactions of New Pregnenedione Derivatives
The in vitro inhibitory activity of five new progesterone derivatives: 17α-hydroxy-16β-methylpregna-1,4,6-triene-3,20-dione 1; 16β-methyl-17α-toluoyloxypregna-1,4,6-triene-3,20-dione 2; 17α-hydroxy-6-methylenepregn-4-ene-3,20-dione 3; 6-methylene-17α-toluoyloxypregn-4ene-3,20-dione 4 and 17α-(p-brom...
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Published in | Chemical & Pharmaceutical Bulletin Vol. 51; no. 10; pp. 1132 - 1136 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English Japanese |
Published |
TOKYO
The Pharmaceutical Society of Japan
01.10.2003
Pharmaceutical Society of Japan Pharmaceutical Soc Japan Maruzen Japan Science and Technology Agency |
Subjects | |
Online Access | Get full text |
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Summary: | The in vitro inhibitory activity of five new progesterone derivatives: 17α-hydroxy-16β-methylpregna-1,4,6-triene-3,20-dione 1; 16β-methyl-17α-toluoyloxypregna-1,4,6-triene-3,20-dione 2; 17α-hydroxy-6-methylenepregn-4-ene-3,20-dione 3; 6-methylene-17α-toluoyloxypregn-4ene-3,20-dione 4 and 17α-(p-bromobenzoyloxy)-6-methylenepregn-4-ene-3,20-dione 5 was determined. These compounds were evaluated as 5α-reductase inhibitors as well as antagonists for the androgen receptor. Compounds 1, 2, 3, 4 and 5 showed the following inhibitory activity for the 5α-reductase enzyme with IC50 values of: 1 (1.65 μM), 2 (10 μM), 3 (19 nM), 4 (100 nM) and 5 (100 nM). The results of this study also showed the effect of increasing concentrations of the novel steroids upon [3H]dihydrotestosterone binding to androgen receptors from male hamster prostate. The Ki values for compounds 1, 2, 3, 4, 5 and dihydrotestosterone showed the following order of affinity for the androgen receptor: 4>5>dihydrotestosterone>2>3>1. The overall data indicated that all synthesized compounds 1, 2, 3, 4 and 5 are inhibitors of the 5α-reductase enzyme present in the hamster prostate. In addition compounds 1, 2, 3, 4 and 5 also presented an affinity for the androgen receptor. |
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ISSN: | 0009-2363 1347-5223 |
DOI: | 10.1248/cpb.51.1132 |