Autor(es): Canário, Catarina ; Matias, Mariana ; Brito, Vanessa ; Pires, Patrícia ; Santos, Adriana O. ; Falcão, Amílcar ; Silvestre, Samuel ; Alves, Gilberto
Data: 2022
Identificador Persistente: https://hdl.handle.net/10316/100517
Origem: Estudo Geral - Universidade de Coimbra
Projeto/bolsa: info:eu-repo/grantAgreement/FCT/UID/Multi/PT;
Assunto(s): C-ring; cytotoxic; docking; estrogenicity; estrone
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. © 2022 by the authors.
