General Papers ARKIVOC 2009 (xiii) 311-323 17-Picolinylidene-substituted steroid derivatives and their antiaromatase and cytotoxic activity Evgenija A. Djurendić, a Jovana J. Ajduković, a* Marija N. Sakač, a Janoš J. Čanadi, a Vesna V. Kojić, b Gordana M. Bogdanović, b and Katarina M. Penov Gaši a a Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia b Oncology Institute of Vojvodina, Institutski put 4, 21204 Sremska Kamenica, Serbia E-mail: jovana.ajdukovic@dh.uns.ac.rs Abstract Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were synthesized. By oxidation of 3β-hydroxy derivative 2 with Jones reagent the corresponding 17(Z)-picolinylidene-androst-4-ene-3,6-dione 4 was obtained. The Oppenauer oxidation of 2 yielded 4-en-3-one derivative 3, which reacted with potassium-t-butoxide in t-butanol to give 4- ene-3,6-dione 4 and 4-hydroxy-4,6-dien-3-one 5 derivatives. Nitration of compound 1 afforded 6-nitro-5-ene derivative 6. The reaction of compound 3 with NaBH 4 in ethanol afforded stereoselectively the 3β-hydroxy-4-ene derivative 7, the acetylation of which gave 3β-acetoxy derivative 8 whereas 17-picolinylidene derivatives 9-14 have been synthesized earlier. Compounds 4-8 were tested on potential inhibitory activity against the enzyme aromatase. Satisfactory inhibitory activity showed compounds 4, 5, 7 and 8. Cytotoxicity in vitro against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231 and prostate cancer AR-, PC-3) and normal fetal lung fibroblasts, MRC-5, of compounds 1-14 was also evaluated. Strong cytotoxic activity showed compound 5 against MDA-MB-231 (IC 50 9.3 µM) and compound 7 against PC-3 (IC 50 10.1 µM). All compounds were not toxic to healthy MRC-5 cells. Keywords: Androstane derivatives, picolinylidene derivatives, aromatase inhibition, cytotoxic activity Introduction Breast cancer is the most commonly diagnosed cancer among women and continues to be a major cause of cancer deaths. 1 There are several approaches for the therapy of breast cancer but the most effective way to treat hormone-dependent breast cancer is to deprive the cancer cells of ISSN 1551-7012 Page 311 © ARKAT USA, Inc. 311