New estrogen receptor antagonists. 3,20-Dihydroxy-19-norpregna-1,3,5(10)-trienes: Synthesis, molecular modeling, and biological evaluation

Kuznetsov, Yu. V.; Левина, И. С.; Scherbakov, Alexander M.; Andreeva, Olga E.; Fedyushkina, I. V.; Dmitrenok, Andrey S.; Shashkov, Alexander S.; Заварзин, И. В.

doi:10.1016/j.ejmech.2017.11.042

Cited by 20 publications

(10 citation statements)

References 31 publications

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“…Kuznestov et al [43], prepared a library of ER- α antagonists based on 3,2′-dihydroxy-19 norpregna-1,3,5 (10)-trienes scaffolds and evaluated their cytotoxicity against MCF-7 cell line using MTT assay. 3,2′-Dihydroxy steroids containing the six-membered ring D´ was found to be the most effective ER α inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Sharma

Kumar

2018

Chemistry Central Journal

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BackgroundCancer is at present one of the leading causes of death in the world. It accounts for 13% of deaths occurred worldwide and is continuously rising, with an estimated million of deaths up to 2030. Due to poor availability of prevention, diagnosis and treatment of breast cancer, the rate of mortality is at alarming level globally. In women, hormone-dependent estrogen receptor positive (ER+) breast cancer making up approximately 75% of all breast cancers. Hence, it has drawn the extensive attention of researchers towards the development of effective drugs for the treatment of hormone-dependent breast cancer. Estrogen, a female sex hormone has a vital role in the initiation and progression of breast malignancy. Therefore, estrogen receptor is the central target for the treatment of breast cancer.ConclusionIn this review, we have studied various classes of antiestrogens that have been designed and synthesized with selective binding for estrogen alpha receptor (ER). Since estrogen receptor α is mainly responsible for the breast cancer initiation and progression, therefore there is need of promising strategies for the design and synthesis of new therapeutic ligands which selectively bind to estrogen alpha receptor and inhibit estrogen dependent proliferative activity.

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Section: Introductionmentioning

confidence: 99%

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Sharma

Kumar

2018

Chemistry Central Journal

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“… Examples include Truncatone A ( I ) derived from the stomata of three xylariaceous fungi belonging to the genus Annulohypoxylon . Furthermore, UT-V167 ( II ) has been identified as a new environmental DNA-encoded metabolite, while compounds III and IV have been reported as new active substances with a strong affinity for the estrogen receptor (ER) . Most methods used to obtain the benzo[ a ]fluorene skeleton require multistep synthesis or separation from natural products. − Therefore, the development of novel synthetic strategies for the construction of benzo[ a ]fluorene skeletons with the readily accessible substrates is expected …”

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confidence: 99%

Radical Tandem Bicyclization Triggered by the α-Position of α,β-Unsaturated Ketones Bearing Nonterminal 1,6-Enynes: Synthesis of the 5H-Benzo[a]fluoren-5-one Skeleton

Zhou

Zhao

et al. 2020

Org. Lett.

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A novel method for the synthesis of 5H-benzo[a]fluoren-5-one from inactive nonterminal 1,6-alkynes through a free radical tandem bicyclization process has been established. This process achieved a continuous cyclization triggered rarely by the α-position of α,β-unsaturated ketones. The reaction constructed three C–C bonds in one step with the readily accessible substrates and excellent substrate compatibility.

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“…Protein expression was determined by immunoblotting [104], reporter analysis used to study the transcriptional activity of oestrogen receptor (ERα) was described in our work [105]. Cell viability was assessed by the MTT test as described in [106].…”

Section: Immunoblotting Reporter Analysis and Mtt-testmentioning

confidence: 99%

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

et al. 2021

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Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

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New estrogen receptor antagonists. 3,20-Dihydroxy-19-norpregna-1,3,5(10)-trienes: Synthesis, molecular modeling, and biological evaluation

Cited by 20 publications

References 31 publications

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Radical Tandem Bicyclization Triggered by the α-Position of α,β-Unsaturated Ketones Bearing Nonterminal 1,6-Enynes: Synthesis of the 5H-Benzo[a]fluoren-5-one Skeleton

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

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