In vivo and in vitro effect of androstene derivatives as 5α-reductase type 1 enzyme inhibitors.
The aim of these studies was to synthesize twelve ester derivatives of dehydroepiandrosterone with therapeutic potential. The effect of 1-12 was demonstrated in the flank organs of gonadectomized hamsters treated with testosterone and the synthesized steroids. In vitro studies were carried out determining the IC50 values for the inhibition of the activity of 5α-reductase type 1 and 2, which are present in rat liver and human prostate respectively. The binding of 1-12 to the androgen receptors (AR) was determined using rat's prostate cytosol. Steroids 1-12 containing different substituents in the phenyl group of the ester moiety in C-3 reduced the flank organs and inhibited the activity of 5α-R type 1; however only steroids 1 and 2 inhibited 5α-R type 2. 1-12 did not bind to the AR. The modification of one atom of the substituents in the phenyl group of the ester moiety in C-3 changed their biological potency (IC50).
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City , Mexico, D. F. , Mexico.
Eugene
E
Bratoeff
Araceli
A
Sánchez
Yazmín
Y
Arellano
Yvonne
Y
Heuze
Juan
J
Soriano
Marisa
M
Cabeza
D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000736:Androstenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D015394:Molecular Structure; D011467:Prostate / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D042944:Cholestenone 5 alpha-Reductase