Synthesis of some epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives and evaluation of their biological activity.
作者： Evgenija Djurendić , Jovana Daljev , Marija Sakač , Janoš Čanadi , Suzana Jovanović Šanta
DOI: 10.1016/J.STEROIDS.2007.09.005
关键词:
摘要: Steroidal epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives have been prepared using 3beta,17beta-dihydroxy-17alpha-picolyl-androst-5-ene (1), 3beta-acetoxy-17-picolinylidene-androst-5-ene (2), 3beta-hydroxy-17-picolinylidene-androst-5-ene (3) as synthetic precursors. The compounds 2 3 were reacted with m-chloroperoxybenzoic acid (MCPBA). synthesized from 17-picolinylidene-N-oxide 4, 5alpha,6alpha-epoxy 5beta,6beta-epoxy-17-picolinylidene-N-oxide 5 6, 5alpha,6alpha:17alpha,20alpha- 5beta,6beta:17alpha,20alpha-diepoxy-N-oxide 7 8. Starting compound 3, a mixture of 5beta,6beta-epoxy-17-picolinylidene 9 10, 11 12, 13 14 obtained. From 15 18, obtained 1 by the Oppenauer oxidation, 4alpha,5alpha-epoxy 4beta,5beta-epoxy 16, 17 20, 21 oxidation 30% H(2)O(2). Oxidation 18 MCPBA yielded only N-oxide 19. structures proved X-ray analysis. Compounds 1-6, 9, 15, 17, tested on activity against enzyme aromatase. Antitumor three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human ER-, MDA-MB-231, prostate cancer PC3) was evaluated. Three (1, 19) showed strong PC3, IC(50) values being in range 0.55-10microM, whereas MDA-MB-231 (IC(50) 10.4microM).
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