26356-54-7Relevant academic research and scientific papers
Design, synthesis, and evaluation of novel 2-methoxyestradiol derivatives as apoptotic inducers through an intrinsic apoptosis pathway
Sheng, Li-Xin,Zhang, Jiang-Yu,Li, Li,Xie, Xiao,Wen, Xiao-An,Cheng, Ke-Guang
, (2020)
In order to discover novel derivatives in the anti-tumor field, reported anti-tumor pharmacophores (uridine, uracil, and thymine) were combined with 2-methoxyestradiol, which has been characterized as having excellent biological properties in terms of anti-tumor activity. Thus, 20 hybrids were synthesized through etherification at the 17β-OH or 3-phenolic hydroxyl group of 2-methoxyestradiol, and evaluated for their biological activities against the human breast adenocarcinoma MCF-7 cell lines, human breast cancer MDA-MB-231 cell lines, and the normal human liver L-O2 cell lines. As a result, all the uridine derivatives and single-access derivatives of uracil/thymine possessed good anti-proliferative activity against tested tumor cells (half maximal inhibitory concentration values from 3.89 to 19.32 μM), while only one dual-access derivative (21b) of thymine possessed good anti-proliferative activity (half maximal inhibitory concentration ≈ 25 μM). Among them, the uridine derivative 11 and the single-access derivative of uracil 12a possessed good anti-proliferative selectivity against tested tumor cells. Furthermore, basic mechanism studies revealed that hybrids 11 and 12a could induce apoptosis in MCF-7 cells through mitochondrial pathway. These hybrids induced morphological changes in MCF-7 cells, causing mitochondrial depolarization. These two hybrids also had the following effects: arrest of the cell cycle at the G2 phase; upregulation of Apaf-1, Bax, and cytochrome c; downregulation of Bcl-2 and Bcl-xL for both mRNA and protein; and increase of the expression for caspase-8 and-9. Finally, apoptotic effector caspase-3 was increased, which eventually caused nuclear apoptosis at least through an intrinsic pathway in the mitochondria. Additionally, hybrids 11 and 12a could specifically bind to estradiol receptor alpha in a dose-dependent manner.
2-METHOXYESTRADIOL DERIVATIVES AND MEDICAL USES THEREOF
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Paragraph 150-154, (2021/04/23)
The present invention relates to novel 2-Methoxyestradiol derivatives and their medical use. In particular, the novel derivatives of the present invention are useful for the treatment or prevention of liver or lung fibrosis. Accordingly, the present inven
Synthesis and biological evaluation of new 2-methoxyestradiol derivatives: Potent inhibitors of angiogenesis and tubulin polymerization
Sun, Moran,Zhang, Yixin,Qin, Jinling,Ba, Mengyu,Yao, Yongfang,Duan, Yongtao,Liu, Hongmin,Yu, Dequan
, (2021/06/15)
Here, we report the structural optimization of a hit natural compound, 2-ME2 (2-methoxyestradiol), which exhibited inhibitory activity but low potency on tubulin polymerization, anti- angiogenesis, MCF-7 proliferation and metastasis in vitro and in vivo. A novel series of 3,17-modified and 17-modified analogs of 2-ME2 were synthesized and investigated for their antiproliferative activity against MCF-7 and another five different human cancer cell lines leading to the discovery of 9i. 9i bind to tubulin colchicine site tightly, inhibited tubulin polymerization and disrupted cellular microtubule networks. Cellular mechanism studies revealed that 9i could induce G2/M phase arrest by down-regulated expression of p-Cdc2, P21 and cell apoptosis by regulating apoptosis-related proteins (Parp, Caspase families) in a dose-dependent manner. Importantly, 9i significantly inhibited HUVEC tube formation, proliferation, migration and invasion. The inhibitory effect against angiogenesis in vivo was confirmed by zebrafish xenograft. Furthermore, 9i could effectively inhibit the proliferation and metastasis of MCF-7 cells in vitro and in zebrafish xenograft. The satisfactory physicochemical property and metabolic stability of 9i further indicated that it can act as a promising and potent anti-angiogenesis, inhibiting proliferation and metastasis of breast cancer agent via targeting tubulin colchicine binding site.
Design, synthesis and biological evaluation of novel 2-methoxyestradiol analogs as dual selective estrogen receptor modulators (SERMs) and antiangiogenic agents
Lao, Kejing,Wang, Yejun,Chen, Mingqi,Zhang, Jingjing,You, Qidong,Xiang, Hua
, p. 390 - 400 (2017/08/22)
2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological e
An efficient, practical synthesis of 2-methoxyestradiol
Xin, Minhang,You, Qidong,Xiang, Hua
experimental part, p. 53 - 56 (2010/09/20)
An efficient and practical scheme to synthesize 2-methoxyestradiol has been developed. The key step was the copper-mediated methoxylation using ethyl acetate as a co-catalyst to introduce a methoxyl group. These synthetic procedures of four steps from 17β-estradiol as starting material gave 2-methoxyestradiol with a 61% overall yield.
Synthesis and structure-activity relationships of 16-modified analogs of 2-methoxyestradiol
Agoston, Gregory E.,Shah, Jamshed H.,LaVallee, Theresa M.,Zhan, Xiaoguo,Pribluda, Victor S.,Treston, Anthony M.
, p. 7524 - 7537 (2008/03/28)
A series of 16-modified 2-methoxyestradiol analogs were synthesized and evaluated for antiproliferative activity toward HUVEC and MDA-MB-231 cells, and for susceptibility to conjugation. In addition, the estrogenicity of these analogs was accessed by meas
17β-HSD1 AND STS INHIBITORS
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, (2010/11/25)
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.
2-Substituted estradiol bis-sulfamates, multitargeted antitumor agents: Synthesis, in vitro SAR, protein crystallography, and in vivo activity
Leese, Mathew P.,Leblond, Bertrand,Smith, Andrew,Newman, Simon P.,Di Fiore, Anna,De Simone, Giuseppina,Supuran, Claudiu T.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
, p. 7683 - 7696 (2007/10/03)
The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast t
A new, practical synthesis of 2-methoxyestradiols.
Rao, Pemmaraju N,Cessac, James W
, p. 1065 - 1070 (2007/10/03)
An efficient and practical approach to synthesize moderate to large amounts of 2-methoxyestradiol (2-ME2) is described. The key step in the synthesis is the regioselective introduction of an acetyl group at the C-2 position of estradiol using a zirconium tetrachloride mediated Fries rearrangement carried out on estradiol diacetate. The seven step synthetic procedure readily gave 2-ME2 in 49% overall yield. Application of this method to the synthesis of 2-methoxy-7 alpha-methylestradiol is also described.
