Synthesis, X-ray crystal structures and biological activity of 16-amino-17-substituted-D-homo steroid derivatives

Penov Gaši, Katarina M.
Miljković, Dušan A.
Medić Mijačević, Ljubica D.
Djurendić, Evgenija A.
Stojanović, Srdjan Z.
Sakač, Marija N.
Djurendić, Maja Dj.
Stanković, Slobodanka M.
Lazar, Dušan
Andrić, Silvana
Kovačević, Radmila

^aDepartment of Chemistry, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 3, Serbia and Montenegro, Yugoslavia
^bDepartment of Physics, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 4, Serbia and Montenegro, Yugoslavia
^cDepartment of Biology, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 2, Serbia and Montenegro, Yugoslavia

^*Corresponding author. Tel.: +381-21-350-122; fax: +381-21-54-065.

Received August 30, 2002; revised March 24, 2003; accepted March 31, 2003.

Steroids 68(8):p 667-676, September 2003. | DOI: 10.1016/S0039-128X(03)00097-7

Abstract

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, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17α-hydroxylase/C17-20 lyase (P450c17) and 17β-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.