ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis, anti-oxidant activity, and cytotoxicity of salicyloyl derivatives of estra-1,3,5(10)-triene and androst-5-ene

Katarina Penov Gaši, Evgenija Djurendić, Sanja Dojčinović-Vujašković, Andrea Gaković, Suzana Jovanović-Šanta, Vesna Kojić, and Marija Sakač

Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia

E-mail: suzana.jovanovic-santa@dh.uns.ac.rs

Abstract: Since many estrane and androstane derivatives exhibit cytotoxic, anti-oxidant, or anti-hormone activity, new steroidal derivatives were synthesised from appropriate estrogen or androgen precursors in order to obtain potential therapeutics for the treatment of steroid-dependent diseases. Starting from estradiol (I), 6-oxo derivatives V and VII were prepared. 17β-Salicyloyl-6-oxo derivatives VI and VIII were synthesised by the reaction of compounds V or VII with methyl salicylate in the presence of sodium. 17β-Salicyloyloxy estradiol IX was prepared from estradiol. Beckmann fragmentation of 16-oxyimino alcohols XII and XIII with methyl salicylate yielded corresponding D-seco derivatives XIV and XV. Simultaneous fragmentation and acylation of compound XII resulted in 3β-salicyloyl-D-seco derivative XVI which was also obtained from compound XIV. Anti-oxidant assays of the newly synthesised compounds V-IX, XIV, and XVI indicated a stronger capacity for hydroxyl radical scavenging, and a weaker capacity for DPPH radical scavenging, compared with the standard anti-oxidants BHA and BHT. Compounds V, XIV, and XVI showed higher or the same activity as BHT. The cytotoxicity of new compounds was evaluated against human breast and prostate carcinoma cells. Compound VI exhibited strong cytotoxicity against MDA-MB-231 cells; compound XIV exhibited strong cytotoxicity against PC-3 cell line, while compound VII moderately inhibited the growth of PC-3 cells.

Keywords: seco-androstane – 6-oxo-estradiol – androst-5-ene – salicyloyl – anti-oxidant activity – cytotoxic activity

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-012-0150-6

Chemical Papers 66 (4) 284–294 (2012)