6298-51-7Relevant articles and documents
Bismuth nitrate-induced novel nitration of estradiol: An entry to new anticancer agents
Bandyopadhyay, Debasish,Rivera, Gildardo,Sanchez, Jorge L.,Rivera, Jesse,Granados, Jose C.,Guerrero, Adrian M.,Chang, Fang-Mei,Dearth, Robert K.,Short, John D.,Banik, Bimal K.
, p. 574 - 583 (2014)
Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells.
Synthesis of 2-[18f]fluoroestradiol, a potential diagnostic imaging agent for breast cancer: Strategies to achieve nucleophilic substitution of an electron-rich aromatic ring with [18f]f
Hostetler, Eric D.,Jonson, Stephanie D.,Welch, Michael J.,Katzenellenbogen, John A.
, p. 178 - 185 (1999)
To improve the pharmacokinetics of fluorine-18 labeled estrogens to be used as receptor-based imaging agents for the identification and staging of estrogen-receptor-positive breast carcinoma, we wanted to synthesize 2- [18F]fluoroestradiol. This compound has high affinity for the estrogen receptor and also binds very well to sex hormone binding globulin, a protein thought to protect estrogens from metabolism and deliver them to target tissues. We anticipated that this compound might have increased tumor uptake and reduced uptake in the liver. The synthesis of a [18F]fluoroaryl estrogen at the high specific activity, no-carrier-added level requires the use of [18F]Fas a precursor. Several strategies were explored for the synthesis of a [18F]fluoroaryl estrogen. The synthesis of 2- [18F]fluoroestradiol was eventually achieved by [18F]fluoride ion displacement of a trimethylammonium leaving group at C-2 of an estrogen, with additional activation being provided by a 6-keto group which was subsequently removed by reduction. Incorporation yields of fluorine-18 were between 20% and 50%. The potential of this new radiopharmaceutical as an imaging agent is being evaluated in an appropriate animal model.
17beta-Estradiol nitration by peroxidase/H2O2/NO2-: a chemical assessment.
Pezzella, Alessandro,Manini, Paola,Di Donato, Paola,Boni, Raffaele,Napolitano, Alessandra,Palumbo, Anna,d'Ischia, Marco
, p. 2927 - 2936 (2007/10/03)
Nitration of 17beta-estradiol by H(2)O(2) and nitrite in the presence of various peroxidases, viz. horseradish peroxidase, lactoperoxidase, and peroxidase-containing homogenates from bovine uteri, was systematically investigated to assess on a chemical basis its potential relevance to the mechanisms of impairment of estrogen functions under oxidative/nitrosative stress conditions. In the presence of excess nitrite 17beta-estradiol reacted smoothly to give 2-nitroestradiol (1), 4-nitroestradiol (2), and 2,4-dinitroestradiol (3). With 10-300 microM estradiol, formation yields of 1-3 were 12-55%, but dropped to 1% or less at lower estrogen concentration, for example, 1 microM, or in plasma as the reaction medium. Time course analysis showed that 2 is the prevalent nitration product under conditions of slow generation of nitrating species, suggesting some regioselectivity for estradiol nitration at C-4, whereas 1 prevails with bolus addition of reagents, due to faster degradation of 2. Competition experiments carried out with (15)NO(2)- showed that 2 is about twice more susceptible to nitration than 1 as determined by (15)N NMR analysis of the resulting 3. The biological effects of 1 and 2 were preliminarily tested on in vitro bovine embryo cultures. When 1 and 2 were substituted to the standard 17beta-estradiol in the oocyte maturation, a significant decrease in both cleavage and blastocyst efficiency was observed in the case of 1 but not 2. Overall, these results suggest that estradiol nitration is a potential pathway of hormonal dysfunction and toxicity but would require elevated estrogen levels of questionable physiological relevance.
