1. C-Ring Oxidized Estrone Acetate Derivatives: Assessment of Antiproliferative Activities and Docking Studies
- Author
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Catarina Canário, Mariana Matias, Vanessa Brito, Patrícia Pires, Adriana O. Santos, Amílcar Falcão, Samuel Silvestre, and Gilberto Alves
- Subjects
estrone ,C-ring ,cytotoxic ,estrogenicity ,docking ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
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.
- Published
- 2022
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