Synthesis, X-ray crystal structures and biological activity of 16-amino-17-substituted-D-homo steroid derivatives.
D-Homo derivatives in the androstane and estrane series, 12-19, were synthesized by a fragmentation-cyclization reaction of 16-oximino-17-hydroxy-17-substituted derivatives 3-9, or by cyclization of the corresponding D-seco derivatives 20-26. The structures were confirmed by X-ray analysis of compounds 12 and 16. Preliminary assessment of inhibitory effects of D-homo derivatives from androstane series towards aromatase, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase/C17-20 lyase (P450c17) and 17 beta-HSD indicated much lower inhibitory potential compared to previously tested activity of another type of D-modified steroids, namely D-seco derivatives. Also, assessment of potential antiestrogenic activity of derivatives from estrane series showed absence of such an activity.
Penov Gasi
Katarina M
KM
Department of Chemistry, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 3, Serbia and Montenegro, Yugoslavia. sazvon@eunet.yu
Miljković
Dusan A
DA
Medić Mijacević
Ljubica D
LD
Djurendić
Evgenija A
EA
Stojanović
Srdjan Z
SZ
Sakac
Marija N
MN
Djurendić
Maja Dj
MDj
Stanković
Slobodanka M
SM
Lazar
Dusan
D
Andrić
Silvana
S
Kovacević
Radmila
R
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000736:Androstenes / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004962:Estranes / Q000737:chemistry / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006718:Homosteroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007985:Leydig Cells / Q000201:enzymology; D008297:Male; D015394:Molecular Structure; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000736:Androstenes; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004962:Estranes; D020847:Estrogen Receptor Modulators; D006718:Homosteroids; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase