Characterization of selective estrogen receptor modulator (SERM) activity in two triarylethylene oxybutyric acids

Rubin, Valeria Norma; Ruenitz, Peter C.; Boyd, Jason; Boudinot, F. Douglas; Wiese, Thomas E.

doi:10.1016/s0006-2952(02)00893-6

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…Plates are read in a fluorometer that can be set to polarization mode. A decrease in fluorescence relative to vehicle control is an indication of binding of a compound to the receptor . At the same time all new derivatives were also tested for estrogen receptor α flash plate assay.…”

Section: Resultsmentioning

confidence: 99%

“…Plates are read in a scintillation counter (Packard Top Count); decreased counts are an indication of binding of a compound to the receptor. The assay was run according to the procedure described by Allan et al , The compounds were then evaluated for its activity in two cell-based functional assays, Ishikawa endometrial cell alkaline phosphatase assay, and MCF-7 breast cancer cell proliferation assay to determine the antagonist activity. The alkaline phosphatase assay in human endometrial Ishikawa cells was run according to the procedure described by Albert et al with minor modification.…”

Section: Resultsmentioning

confidence: 99%

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Identification and Structure−Activity Relationships of Chromene-Derived Selective Estrogen Receptor Modulators for Treatment of Postmenopausal Symptoms

Jain

Kanojia

et al. 2009

J. Med. Chem.

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As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), novel chromene scaffolds, benzopyranobenzoxapanes, were discovered. Many compounds showed binding affinity as low as 1.6-200 nM, displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line as well in Ishikawa cell line with IC(50) values in the range 0.2-360 nM. On the basis of the side chain substitution, various compounds demonstrated strong inhibitory activity in anti-uterotropic assay. Compound 7-(R) and its major metabolites 5-(R) and 6-(R) were evaluated in several in vivo models of estrogen action. Relative to a full estrogen agonist (ethynyl estradiol) and the SERM raloxifene, 7-(R) was found to be a potent SERM that behaved as antagonist in the uterus and exhibited estrogen agonistic activity on bone, plasma lipids, hot flush, and vagina. The overall pharmacokinetic profile and stability were significantly improved compared to those of the phase 2 development compound 9-(R).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Identification and Structure−Activity Relationships of Chromene-Derived Selective Estrogen Receptor Modulators for Treatment of Postmenopausal Symptoms

Jain

Kanojia

et al. 2009

J. Med. Chem.

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“…The culture and assay conditions for the cell lines, MVLN and MCF-7 subclone E3, have been previously described (Wiese et al 1992;Rubin et al 2002). Briefiy, cultures were maintained in phenol red free Dulbecco's Modified Eagle's Medium with 10% fetal bovine serum (FBS) (HyClone, Logan, UT) and passed weekly.…”

Section: Bioassay Methodsmentioning

confidence: 99%

Removal of estrogens and estrogenicity through drinking water treatment

Schenck

Rosenblum²,

Wiese

et al. 2011

Journal of Water and Health

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Estrogenic compounds have been shown to be present in surface waters, leading to concerns over their possible presence in finished drinking waters. In this work, two in vitro human cell line bioassays for estrogenicity were used to evaluate the removal of estrogens through conventional drinking water treatment using a natural water. Bench-scale studies utilizing chlorine, alum coagulation, ferric chloride coagulation, and powdered activated carbon (PAC) were conducted using Ohio River water spiked with three estrogens, 17β-estradiol, 17α-ethynylestradiol, and estriol.Treatment of the estrogens with chlorine, either alone or with coagulant, resulted in approximately 98% reductions in the concentrations of the parent estrogens, accompanied by formation of by-products. The MVLN reporter gene and MCF-7 cell proliferation assays were used to characterize the estrogenic activity of the water before and after treatment. The observed estrogenic activities of the chlorinated samples showed that estrogenicity of the water was reduced commensurate with removal of the parent estrogen. Therefore, the estrogen chlorination by-products did not contribute appreciably to the estrogenic activity of the water. Coagulation alone did not result in significant removals of the estrogens. However, addition of PAC, at a typical drinking water plant dose, resulted in removals ranging from approximately 20 to 80%.

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“…On the other hand, there are only limited reports concerning the replacement of the ether moiety (Lubczyk et al, 2002 ), including the straightforward syntheses of numerous N-substituted TAM derivatives (Ahmed et al, 2016 ) containing a carbonyl group directly connected to the phenol C-ring. These compounds were determined to display selective estrogenic activities combined with good binding affinities to the ER (Rubin et al, 2001 , 2002 ; Nguyen et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

et al. 2017

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Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER) binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

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Characterization of selective estrogen receptor modulator (SERM) activity in two triarylethylene oxybutyric acids

Cited by 5 publications

References 39 publications

Identification and Structure−Activity Relationships of Chromene-Derived Selective Estrogen Receptor Modulators for Treatment of Postmenopausal Symptoms

Identification and Structure−Activity Relationships of Chromene-Derived Selective Estrogen Receptor Modulators for Treatment of Postmenopausal Symptoms

Removal of estrogens and estrogenicity through drinking water treatment

Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

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