Collect. Czech. Chem. Commun. 2008, 73, 627-636

Synthesis and Biological Evaluation of Some A,D-Ring Modified 16,17-Secoandrostane Derivatives

Evgenija A. Djurendića, Marina P. Zaviša, Marija N. Sakača,*, Vesna V. Kojićb, Gordana M. Bogdanovićb and Katarina M. Penov Gašia

a Department of Chemistry, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 3, Serbia
b Oncology Institute of Vojvodina, Institutski put 4, 21204 Sremska Kamenica, Serbia


Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 2-11 were synthesized. Protection of the 17-oxo function of compound 1 with ethylene glycol yielded compounds 2 and 3. The Oppenauer oxidation of 2 or oxidation with H2O2 in alkaline conditions gave the respective compounds 4 and 10. Epoxidation of compound 4 yielded a mixture of 4α,5α- and 4β,5β-epoxides 5 and 6 and a mixture of 4α,5α- and 4β,5β-epoxy-carboxamides 7 and 8. Opening of the oxirane ring of a mixture of compounds 5 and 6 with formic acid afforded the 4-hydroxy derivative 9. Anti-aromatase activity and in vitro cytotoxicity for three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231, and prostate cancer, PC3) of selected compounds were evaluated. Compounds 2, 4, 9, and 10 showed a strong cytotoxicity for PC3 cells.

Keywords: 16,17-Secosteroids; 4-En-3-one steroids; Androstane derivatives; Anti-aromatase activity; In vitro cytotoxicity.

References: 14 live references.