Synthesis and antitumor activity of new D-seco and D-homo androstane derivatives.
Starting from 3beta-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3beta-hydroxy-17-oxa-D-homoandrost-5-ene-16-one (10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, prostate cancer AR-, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC(50) values being 2 microM and 0.55 microM, respectively. Compounds 6 (10 microM) and 14 (9 microM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5.
Djurendić
Evgenija A
EA
Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
Zavis
Marina P
MP
Sakac
Marija N
MN
Canadi
Janos J
JJ
Kojić
Vesna V
VV
Bogdanović
Gordana M
GM
Penov Gasi
Katarina M
KM
D000731:Androstanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50
D000731:Androstanes; D000970:Antineoplastic Agents; C033936:androstane