Molecular interactions of new pregnenedione derivatives.
The in vitro inhibitory activity of five new progesterone derivatives: 17alpha-hydroxy-16beta-methylpregna-1,4,6-triene-3,20-dione 1; 16beta-methyl-17alpha-toluoyloxypregna-1,4,6-triene-3,20-dione 2; 17alpha-hydroxy-6-methylenepregn-4-ene-3,20-dione 3; 6-methylene-17alpha-toluoyloxypregn-4ene-3,20-dione 4 and 17alpha-(p-bromobenzoyloxy)-6-methylenepregn-4-ene-3,20-dione 5 was determined. These compounds were evaluated as 5alpha-reductase inhibitors as well as antagonists for the androgen receptor. Compounds 1, 2, 3, 4 and 5 showed the following inhibitory activity for the 5alpha-reductase enzyme with IC(50) values of: 1 (1.65 microM), 2 (10 microM), 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 [(3)H]dihydrotestosterone binding to androgen receptors from male hamster prostate. The K(i) 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 5alpha-reductase enzyme present in the hamster prostate. In addition compounds 1, 2, 3, 4 and 5 also presented an affinity for the androgen receptor.
Bratoeff
Eugene
E
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City.
Ramírez
Elena
E
Flores
Eugenio
E
Valencia
Norma
N
Sánchez
Mauricio
M
Heuze
Ivonne
I
Cabeza
Marisa
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D011374:Progesterone / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase