Steroid nitrates. II. Synthesis and hormonal activity of 9α,11β-dihydroxyestra-1,3,5(10)-triene 11-nitrates

Abstract

11-Nitrates of 9a,11b-dihydroxy derivatives of estrone, estradiol, and ethinylestradiol were synthesized by oxidative nitration of the corresponding estratriene 3-acetates with cerium ammonium nitrate. Three methods are given for this reaction. Compounds had high antifertility and estrogen activity. Antifertility actions were much greater than their estrogen activities, as compared with the similar levels seen with ethinylestradiol.

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies

“…In fact, OMATE had a stimulatory effect (0.15 g ± 0.01) on the uterine growth in ovariectomized rats, which was approximately 50% higher than that of EMATE (0.11 g ± 0.02) [ 8 ]. In addition, and as previously referred, despite that 9α-hydroxy,11β-nitrooxyestrone-17-oxime had relevant anti-breast cancer effects, this compound also stimulated the tumor growth after a 15-day treatment period [ 25 ]. This preliminary study seemed to suggest the estrogenic activity of compound 11 .…”

“…The introduction of halogens (compounds 7 and 9 ) and of Δ 9,11 double bond (compound 8 ) were effected using methodologies already applied by us [ 28 ]. Finally, for the preparation of oximes we selected a method involving the use of EtOH, NaOH and hydroxylamine hydrochloride [ 8 ] as this is a more selective and greener strategy than other approaches that use, for example, pyridine [ 25 ]. In fact, these methods involve more toxic reagents/solvents, are more time consuming, have complex workups and can lead to lower reaction yields [ 31 , 32 , 33 ].…”

“…In addition, these compounds also inhibited tubulin polymerization and had low binding affinities to ERα [ 17 , 24 ]. In estrane steroids, Rzheznikov and co-workers [ 25 ] synthesized 9α-hydroxy,11β-nitrooxyestrone-17-oxime and evidenced in vivo its antitumor effect against breast cancers. However, when compared with the corresponding 17-ketone analogue, the presence of the oxime group seemed to have low influence in this activity.…”

“…However, when compared with the corresponding 17-ketone analogue, the presence of the oxime group seemed to have low influence in this activity. In addition, these two compounds stimulated the tumor growth by the end of a 15-day treatment course, possibly due to their estrogenic effects [ 25 ]. Concerning substituted oximes, a large number of estrone-16-oxime ethers were synthesized and their antiproliferative effects were in vitro evaluated against several cell lines.…”