Synthesis and biochemical evaluation of the novel steroid androsta-4,6,8(9)-triene-3,17-dione.
According to a proposed aromatisation mechanism by which estrogens are biosynthesized from androgens, the novel steroid androsta-4,6,8(9)-triene-3,17-dione (FCE 24918) should behave as a suicide substrate for aromatase. The synthesis of this triene steroid has been accomplished starting from androsta-4,7-diene-3,17-dione (4) by the acid-catalysed cleavage of the corresponding 7,8 alpha-epoxide, 5, and it was obtained together with androsta-4,6,8(14)-triene-3,17-dione (FCE 24917) as a side product. The time-dependent inactivation of placental aromatase by the two isomers was studied comparatively and showed that the 4,6,8(9)-triene moiety acts as a latent alkylating group.
Panzeri
A
A
Farmitalia Carlo Erba, Research and Development, Milano, Italy.
Ornati
G
G
di Salle
E
E
Lombardi
P
P
D000733:Androstatrienes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013329:Structure-Activity Relationship
D000733:Androstatrienes; D047072:Aromatase Inhibitors; C069517:androsta-4,6,8(9)-triene-3,17-dione