Delta(9,11)-Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

Canario, Catarina; Matias, Mariana; de Brito, Vanessa; Santos, Adriana O.; Falcao, Amilcar; Silvestre, Samuel ✉; Alves, Gilberto

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
Megjelent: COMPTES RENDUS CHIMIE 1631-0748 1878-1543 23 (2) pp. 201-217 2020
  • SJR Scopus - Chemical Engineering (miscellaneous): Q2
    A series of Delta(9,11)-estrone derivatives with A- and D-ring modifications has been synthesized and evaluated as antiproliferative agents. The cytotoxicity was assessed in six cell lines (MCF-7, T47-D, LNCaP, llepaRG, Caco-2 and NUM.) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and a cell cycle distribution analysis was performed by flow cytometry. Some compounds exhibited relevant cytotoxicity, particularly Delta(9,11)-estrone, which was the most active against llepaRG cells (IC50 = 6.67 mu M). Besides the relevance of the double bond in the C-ring, the presence of a 16E-benzylidene group increased the antiproliferative effect on MCF-7 and T47-D cells. Moreover, the introduction of iodine in positions 2 and 4 of estrone seemed to induce a selective cytotoxicity for I lepaRG cells. Flow cytometry experiments evidenced a 34% reduction of HepaRG cell viability after treatment with Delta(9,11)-estrone and a cell cycle arrest at the G(0)/G(1) phase. Estrogenic activity was also observed for this compound at 0.1 mu M in T47-D cells, and molecular docking studies estimated a marked interaction between this compound and the estrogen receptor alpha.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
    2021-05-14 14:22