- Synthesis, anti-oxidant activity, and cytotoxicity of salicyloyl derivatives of estra-1, 3, 5(10)-triene and androst-5-ene
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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 Dseco 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.
- Gasi, Katarina Penov,Djurendic, Evgenija,Dojcinovic-Vujaskovic, Sanja,Gakovic, Andrea,Jovanovic-Santa, Suzana,Kojic, Vesna,Sakac, Marija
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scheme or table
p. 284 - 294
(2012/08/28)
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- 17β-HSD1 AND STS INHIBITORS
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The present invention relates to novel substituted steroid derivatives which represent selectiv inhibitors of the 17β-hydroxysteroid dehydrogenase type I (17β-HSD1) and, in addition, which may represent inhibitors of the steroid sulphatase, as well as to their salts, to pharmaceutical preparations containing these compounds and to processes for the preparation of these compounds. Furthermore, the invention concerns the therapeutic use of said novel substituted steroid derivatives, particularly their use in the treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase type I and/or steroid sulphatase enzymes and/or requiring the lowering of the endogenous 17β-estradiol concentration.
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Page/Page column 88-89
(2010/11/25)
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