60788-62-7Relevant articles and documents
New estrone oxime derivatives: Synthesis, cytotoxic evaluation and docking studies
Alves, Gilberto,Brito, Vanessa,Canário, Catarina,Falc?o, Amílcar,Matias, Mariana,Santos, Adriana O.,Silvestre, Samuel
, (2021/05/26)
The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehy-drogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the ?9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G2 /M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between ?9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.
?9,11-Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies
Alves, Gilberto,Canário, Catarina,Falc?o, Amílcar,Matias, Mariana,Santos, Adriana O.,Silvestre, Samuel,de Brito, Vanessa
, p. 211 - 217 (2021/06/25)
A series of ?9,11-estrone derivatives with A- and D-ring modifications has been synthesized and evaluated as antiproliferative agents. The cytotoxicity was assessed in six cell lines (MCF-7, T47-D, LNCaP, HepaRG, Caco-2 and NHDF) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and a cell cycle distribution analysis was performed by flow cytometry. Some compounds exhibited relevant cytotoxicity, particularly ?9,11-estrone, which was the most active against HepaRG cells (IC50 = 6.67 μM). Besides the relevance of the double bond in the C-ring, the presence of a 16E-benzylidene group increased the antiproliferative effect on MCF-7 and T47-D cells. Moreover, the introduction of iodine in positions 2 and 4 of estrone seemed to induce a selective cytotoxicity for HepaRG cells. Flow cytometry experiments evidenced a 34% reduction of HepaRG cell viability after treatment with ?9,11-estrone and a cell cycle arrest at the G0/G1 phase. Estrogenic activity was also observed for this compound at 0.1 μM in T47-D cells, and molecular docking studies estimated a marked interaction between this compound and the estrogen receptor α.
Chemoselective Suzuki-Miyaura reactions of 4-bromo-3-O-triflyl-estrone. Synthesis and atropisomerism of arylated estrones
Jopp, Stefan,Wallaschkowski, Tina,Ehlers, Peter,Frank, Eva,Schneider, Gyula,W?lfling, János,Mernyák, Erzsébet,Villinger, Alexander,Langer, Peter
, p. 2825 - 2836 (2018/05/04)
4-Bromo-3-O-triflyl-estrone has been synthesized in 2 steps from estrone and was successfully employed in chemoselective palladium catalysed Suzuki-Miyaura reactions. Mono- and bis-arylations were carried out selectively by variation of ligands and solven
