Determination of rat 5alpha-reductase type 1 isozyme activity and its inhibition by novel steroidal oxazolines.
The 5alpha-reductase type 1 isozyme is a key enzyme in the metabolism of the androgen steroid hormones and inhibitors of this enzyme represent a new pharmacological treatment for several androgen dependent diseases. We developed a radiosubstrate in vitro incubation method for the determination of 5alpha-reductase type 1 activity using rat liver microsomes as an enzyme source. With this method we have studied the inhibiting activity of novel (5' S)-17beta-(4,5-dihydrooxazol-5-yl)androst-5-en-3-one compounds containing various derivatized phenyl substituents coupled to the exo -heterocyclic moiety. Tests revealed moderate inhibitory actions compared to finasteride, nevertheless, results provide interesting structure-activity relationship data.
Szécsi
M
M
1st Department of Medicine, University of Szeged, 8-10 H-6720 Szeged, Hungary. szecsim@endoc.szote.u-szeged.hu
Ondré
Dóra
D
Tóth
I
I
Magony
S
S
Wölfling
J
J
Schneider
Gy
G
Julesz
J
J
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis* / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000736:Androstenes / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001378:Azasteroids / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D018120:Finasteride / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D001378:Azasteroids; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010080:Oxazoles; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase