Chemical synthesis of C3-oxiranyl/oxiranylmethyl-estrane derivatives targeted by molecular modeling and tested as potential inhibitors of 17β-hydroxysteroid dehydrogenase type 1

Lespérance, Maxime; Barbeau, Xavier; Roy, Jenny; Maltais, René; Lagüe, Patrick; Poirier, Donald

doi:10.1016/j.steroids.2018.09.009

Cited by 3 publications

(2 citation statements)

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“…Molecular docking studied the interactions between these C-ring oxidized E1 acetate analogs and proteins that interact with them [66,67]. Few studies were reported, including docking with C-ring modified steroids [21,68].…”

Section: Discussionmentioning

confidence: 99%

C-Ring Oxidized Estrone Acetate Derivatives: Assessment of Antiproliferative Activities and Docking Studies

et al. 2022

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C-Ring oxidized estrone acetate derivatives as antiproliferative agents were prepared and tested against five cancer cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry assays to evaluate cell viability and modifications in cell cycle phases and molecular docking research against estrogen receptor α, steroid sulfatase, and 17β-hydroxysteroid dehydrogenase type 1 were performed. 9α-Hydroxy,11β-nitrooxyestrone acetate was the most cytotoxic molecule against hormone-dependent cancer cells. Furthermore, flow cytometry experiments revealed that this 9α-hydroxy,11β-nitrooxy derivative markedly reduced HepaRG cells viability (~92%) after 24 h of treatment. However, 9α-hydroxyestrone acetate led to selective inhibition of HepaRG cells growth, inducing a G0/G1 cycle arrest, and did not originate a proliferation effect on T47-D cancer cells. Docking studies estimated a generally lower affinity of these compounds to estrogen receptor α than predicted for estrone and 17β-estradiol. Therefore, this structural modification can be of interest to develop new anticancer estrane derivatives devoid of estrogenic action.

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Section: Discussionmentioning

confidence: 99%

C-Ring Oxidized Estrone Acetate Derivatives: Assessment of Antiproliferative Activities and Docking Studies

et al. 2022

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“…However, those inhibitors exhibit some detrimental side effects, which is the reason why research continues on this topic. 17β-Hydroxysteroid dehydrogenase (17β-HSD) [ 24 , 25 ], sulfatase (STS) [ 26 ], as well as sulfotransferase (SULT) [ 27 ] have also been taken under close consideration using molecular modelling in order to contribute to anti-cancer drug development. The first of the two enzymes transforms estrone into estradiol.…”

Section: Introductionmentioning

confidence: 99%

Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens

Mazurek

Szeleszczuk

Simonson

et al. 2020

IJMS

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In this review, applications of various molecular modelling methods in the study of estrogens and xenoestrogens are summarized. Selected biomolecules that are the most commonly chosen as molecular modelling objects in this field are presented. In most of the reviewed works, ligand docking using solely force field methods was performed, employing various molecular targets involved in metabolism and action of estrogens. Other molecular modelling methods such as molecular dynamics and combined quantum mechanics with molecular mechanics have also been successfully used to predict the properties of estrogens and xenoestrogens. Among published works, a great number also focused on the application of different types of quantitative structure–activity relationship (QSAR) analyses to examine estrogen’s structures and activities. Although the interactions between estrogens and xenoestrogens with various proteins are the most commonly studied, other aspects such as penetration of estrogens through lipid bilayers or their ability to adsorb on different materials are also explored using theoretical calculations. Apart from molecular mechanics and statistical methods, quantum mechanics calculations are also employed in the studies of estrogens and xenoestrogens. Their applications include computation of spectroscopic properties, both vibrational and Nuclear Magnetic Resonance (NMR), and also in quantum molecular dynamics simulations and crystal structure prediction. The main aim of this review is to present the great potential and versatility of various molecular modelling methods in the studies on estrogens and xenoestrogens.

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Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors

Poirier

2025

Steroids

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Chemical synthesis of C3-oxiranyl/oxiranylmethyl-estrane derivatives targeted by molecular modeling and tested as potential inhibitors of 17β-hydroxysteroid dehydrogenase type 1

Cited by 3 publications

References 28 publications

C-Ring Oxidized Estrone Acetate Derivatives: Assessment of Antiproliferative Activities and Docking Studies

C-Ring Oxidized Estrone Acetate Derivatives: Assessment of Antiproliferative Activities and Docking Studies

Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens

Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors

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