Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and Its Analogues

Abstract

The natural product ferutinin was shown to act as an agonist to estrogen receptor ERα and agonist/antagonist to ERβ featuring a weak antiproliferative activity toward breast cancer cells. To enhance this activity, ferutinin analogues were synthesized by esterification of jaeschkenadiol with different acids. These compounds were assayed for their in vitro antiproliferative activity against estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cell lines. Among the compounds, 3c' exhibited a potent inhibitory selective activity against MCF-7 with IC50 value of 1 μm. Docking simulation of 3c' in the ligand binding domain of the ERs indicated a potential antagonism interaction with both ER subtypes. Functional assay showed that 3c' binds as an antagonist to ERα protein while ferutinin acts as an agonist. © 2015 John Wiley & Sons A/S.