Microwave-assisted synthesis, characterization and cytotoxic studies of novel estrogen receptor alpha ligands towards human breast cancer cells

摘要

A new, simple, and microwave-assisted, solution-phase T3P (R)-DMSO mediated method for the preparation of a novel class of estrogen receptor alpha (ER alpha) ligands based on the 2-phenylquinoline scaffold was developed. Furthermore, the novel ER alpha ligands were tested for their bioactivity against ER alpha-positive and ER alpha-negative cell lines. The ligand (entry 4), with amine and nitro group substitution at C4 position, displayed significant cytotoxicity against MCF-7 and HepG2 cells with an IC50 value of 6 and 11 mu M, respectively. On the other hand, ER alpha-negative cells displayed resistance to quinolines induced cytotoxicity with an IC50 value >100 Mm and they does not induce cytotoxicity in normal breast epithelial cells. Molecular docking analyses suggest a consistent binding mode for these ER alpha ligands in the ligand binding domain of the human ER alpha and predict the ligands to occupy the hydrophobic cavity in a similar fashion as estradiol or GW2368. (C) 2015 Elsevier Ltd. All rights reserved.