- Synthesis and Antitumor Evaluation of Novel Hybrids of Phenylsulfonylfuroxan and Estradiol Derivatives
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Fifteen novel furoxan-based nitric oxide (NO) releasing hybrids of estradiol derivatives were synthesized and evaluated in vitro anti-proliferative activity in MDA-MB-231, A2780, Hela and HUVEC cell lines. Most of them displayed potent anti-proliferative effects. Among the compounds, 4-bromo-3-((phenylsulfonyl)-1,2,5-oxadiazole 2-oxide)-oxy-propoxy-estradiol (11 b) exhibited the best activity with IC50 values of 3.58–0.0008 μM. Preliminary pharmacological studies showed that 11 b induced apoptosis and hardly affected the cell cycle of MDA-MB-231 cell line. NO-releasing capacity and inhibition of ERK/MAPK pathway signaling might explain the potent antineoplastic activity of these compounds. The preliminary structure-activity relationship (SAR) showed that steroidal scaffolds with a linker in 3-position were favorable moieties to evidently increase the bioactivities of these hybrids. Overall, these results implied that 11 b merited to be further investigated as a promising anti-cancer candidate.
- Wan, Qi,Deng, Yan,Huang, Yaoqing,Yu, Zhihui,Wang, Chunli,Wang, Ke,Dong, Jibin,Chen, Ying
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- Cross-coupling of [11C]methyllithium for 11C-labelled PET tracer synthesis
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The cross-coupling of aryl bromides with [11C]CH3Li for the labelling of a variety of tracers for positron emission tomography (PET) is presented. The radiolabelled products were obtained in excellent yields, at rt and after short reaction times (3-5 min) compatible with the half-life of 11C (20.4 min). The automation of the protocol on a synthesis module is investigated, representing an important step towards a fast method for the synthesis of 11C-labelled compounds for PET imaging. This journal is
- Helbert, Hugo,Antunes, Ines Farinha,Luurtsema, Gert,Szymanski, Wiktor,Feringa, Ben L.,Elsinga, Philip H.
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supporting information
p. 203 - 206
(2021/01/13)
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- Estradiol derivative as well as preparation method and application thereof
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The invention relates to the technical field of organic synthesis and discloses an estradiol derivative as well as a preparation method and application thereof. The estradiol derivative has a structure shown in a formula 1. An estradiol 4 site is modified and coupled with 3-sulfydryl/hydroxyl/amino propionic acid to form a novel derivative containing carboxyl at estradiol 4 site, and compared withan estradiol 3 site derivative, the derivative has better specificity and accuracy, shows good gradient, has a good reaction effect as an antigen and has higher economic value.
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Paragraph 0019; 0031; 0032; 0037; 0038; 0043; 0044
(2020/03/06)
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- 18F-labelling of A-ring substituted 16α-fluoro-estradiols as potential radiopharmaceuticals for PET imaging
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The 2-methoxy derivative of estradiol is currently in Phase II clinical trial as an anticancer agent while the 4-methyl derivative has been shown to interact with cytoplasmic and nuclear estrogen receptors in rat pituitary gland and hypothalamus. We hypothesize that the 16α-18F-analogs of these estrogens could be suitable radiotracers to evaluate action mechanisms of the parent compounds. In this study we report the synthesis of the 16α-18F and 16α-19F-analogs of the A-ring substituted estradiols in high yield via stereoselective opening of the intermediate 16β,17β-O-cyclic sulfones with [18F]F- or F- followed by deprotection.
- Ahmed, Naseem,Garcia, Guillaume,Ali, Hasrat,van Lier, Johan E.
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scheme or table
p. 42 - 50
(2009/04/10)
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- Electrochemical A-ring bromination of estrogens
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A-ring bromination of estrogens has been achieved by constant current electrolysis of the solutions of these substrates and Et4NBr in appropriate solvents. Thus, electrolysis consuming 2 F mol-1 charge gave mixtures of 2- and 4-estrogens (1:1.1-2.5; up to 97%), whereas 4 F mol -1 charge experiments yielded 2,4-dibromoestrogens as the sole products.
- Damljanovic, Ivan,Vukicevic, Mirjana,Vukicevic, Rastko D.
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p. 407 - 409
(2008/02/11)
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- Chemical synthesis of six novel 17β-estradiol and estrone dimers and study of their formation catalyzed by human cytochrome P450 isoforms
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Our earlier studies have shown that over 20 nonpolar 17β-estradiol metabolite peaks were detected following incubations of radioactive 17β-estradiol with human liver microsomes or recombinant human cytochrome P450 isoforms in the presence of NADPH as a co
- Chen, Aaron Yun,Lee, Anthony J.,Jiang, Xiang-Rong,Bao, Ting Zhu
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p. 5372 - 5381
(2008/03/13)
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- Estrogen conjugation and antibody binding interactions in surface plasmon resonance biosensing
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Thioether-linked 3-mercaptopropionic acid derivatives of 17β-estradiol and estrone were formed at the A-ring 4-position of the steroids by substitution of their 4-bromo analogues. The carboxylic acid terminal was used to link to an oligoethylene glycol (OEG) chain of 15-atoms in length. The OEG derivative of 17β-estradiol was then in situ immobilized on a carboxymethylated dextran-coated gold sensor surface used to detect refractive index changes upon protein binding to the surface by surface plasmon propagation in a BIAcore surface plasmon resonance (SPR) instrument. Two other estradiol-OEG derivatives with Mannich reaction linkage at the 2-position and hemisuccinate linkage at the 3-position were also immobilized on the sensor surfaces for comparison. Binding performance between these immobilized different positional conjugates and monoclonal anti-estradiol antibody, raised from a 6-position conjugate, clearly demonstrated that both 2- and 4-conjugates, not conjugated through existing functional groups, gave strong antibody bindings, whereas the 3-conjugate through an existing functional group (3-OH) gave very little binding (2% compared to the 2-conjugate). Both 2- and 4-position conjugates were then applied in a highly sensitive estradiol SPR immunoassay with secondary antibody mediated signal enhancement that gave up to a 9.5-fold signal enhancement of primary antibody binding, and a detection limit of 25 pg/mL was achieved for a rapid and convenient flow-through immunoassay of estradiol.
- Mitchell, John S.,Wu, Yinqiu,Cook, Christian J.,Main, Lyndsay
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p. 618 - 631
(2007/10/03)
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- Chemical synthesis of two novel diaryl ether dimers of estradiol-17β
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We recently detected the formation of estradiol-17β (estradiol) dimers, linked together through a diaryl ether bond between the C-3 phenolic oxygen of one estradiol molecule and the 2- or 4-position aromatic carbon of another estradiol, following incubations of [3H]estradiol with human liver microsomes or cytochrome P450 enzymes in the presence of NADPH. Using estradiol as the starting material, we designed a four-step method for the chemical synthesis of these two estrogen dimers with the Ullmann condensation reaction as a key step. Step 1: Synthesis of 2- or 4-bromoestradiol from estradiol. Step 2: Protection of the C-3 phenolic hydroxyl group of the 2- or 4-bromoestradiol. Step 3: The Ullmann condensation reaction between the phenol-protected bromoestradiol and the estradiol potassium salt under our modified reaction conditions (with a 41% product yield). Step 4: Removal of the C-3 benzyl group by catalytic hydrogenation. The chromatographic and various spectrometric properties of the two synthesized compounds were identical to those metabolically formed by human cytochrome P450 3A4.
- Lee, Anthony J.,Sowell, J. Walter,Cotham, William E.,Zhu, Bao Ting
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- Reaction of Benzeneselenyl Halides with Estrogens
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The reaction of estradiol and estrone with benzeneselenyl chloride affords mainly 2-phenylselenyl adducts which are readily converted into the corresponding 2-halogenated estrogens upon treatment with a variety of reagents.
- Ali, Hasrat,Lier, Johan E. van
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p. 269 - 271
(2007/10/02)
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- A NEW SYNTHETIC ROUTE TO 2- AND 4-METHOXYESTRADIOLS BY NUCLEOPHILIC SUBSTITUTION
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A new synthetic route to 2- and 4-methoxyestradiols is described.Benzo-15-crown-5 with CuI catalyzes the specific nucleophilic substitution at the carbon atom carrying a non-activated halogen on ring A of the estradiol.
- Chen, Shu-hua,Luo, Guan-rong,Wu, Xu-sen,Chen, Min,Zhao, Hua-ming
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- Synthesis of 2-Methoxy- and 4-Methoxy-Estrogens with Halogen-Methoxy Exchange Reaction
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Synthesis of 2-methoxy- and 4-methoxy-estrone (6) and (9), 2-methoxy- and 4-methoxy-estradiol (15) and (18), and 2-methoxy- and 4-methoxy-estratriol (24) and (27) are described.Catalytic hydrogenation over Pd/C of 2,4-dibromo or 2,4-diiodo estrogens gave regioselectively the corresponding 4-halogeno derivatives in excellent yields.Reaction of 2-iodo or 4-iodo estradiol and 2-iodo or 4-iodo estriol with NaOCH3 in MeOH and dimethylformamide (DMF) in the presence of CuCl2 gave in an excellent yield and in a good yield, while (6) and (9) were also similarly obtained by the reaction with pyridine instead of DMF.
- Numazawa, Mitsuteri,Ogura, Yuko,Kimura, Katsuhiko,Nagaoka, Masao
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p. 3701 - 3715
(2007/10/02)
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- Efficient Synthesis of 2-Methoxy- and 4-Methoxy-estrogens
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2-Methoxy- and 4-methoxy-estrogens are easily prepared from the corresponding 2-iodo or 4-bromo derivatives in high yields by a halogen-methoxy group exchange reaction using sodium methoxide-copper(II) chloride.
- Numazawa, Mitsuteru,Ogura, Yuko
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p. 533 - 534
(2007/10/02)
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