Inhibitory effects of fluorine-substituted estrogens on the activity of 17beta-hydroxysteroid dehydrogenases.
In search for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (h17beta-HSD1) a specific group of steroids with interesting properties including novel compounds was investigated. Several estratriene derivatives with fluorine-substitution in position 17 of the steroidal scaffold were synthesised and tested in vitro towards recombinant h17beta-HSD1, 2, 4, 5 and 7. Moderate, mostly unselective inhibitors of h17beta-HSD1 and h17beta-HSD2 and a selective inhibitor of h17beta-HSD5 were identified. The structure-activity relationship with respect to inhibitory strengths and selectivity of these compounds on five h17beta-HSDs is discussed.
Deluca
Dominga
D
GSF-National Research Center for Environment and Health, Institute of Experimental Genetics, Genome Analysis Center, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Möller
Gabriele
G
Rosinus
Andrea
A
Elger
Walter
W
Hillisch
Alexander
A
Adamski
Jerzy
J
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004963:Estrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004963:Estrenes; D004967:Estrogens; D005461:Fluorine; D015067:17-Hydroxysteroid Dehydrogenases