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

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 molec...

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Published in:Applied sciences 2022-04, Vol.12 (7), p.3579
Main Authors: Canário, Catarina, Matias, Mariana, Brito, Vanessa, Pires, Patrícia, Santos, Adriana O., Falcão, Amílcar, Silvestre, Samuel, Alves, Gilberto
Format: Article
Language:English
Subjects:
17β-Estradiol
Acetic acid
Antiproliferatives
C-ring
Cancer
Cell cycle
Cell division
Cell proliferation
Cell viability
Chromatography
cytotoxic
Cytotoxicity
docking
Estrogen receptors
estrogenicity
Estrogens
Estrone
Flow cytometry
Gene expression
Hydroxysteroids
Molecular docking
NMR
Nuclear magnetic resonance
Solvents
Steroid sulfatase
Steroids
Tumor cell lines
Xenoestrogens
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Summary: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.
ISSN:2076-3417
2076-3417
DOI:10.3390/app12073579