Diarylether-Amino Acid Conjugates as New Class of Anticancer Agents

Diarylether (DE) is a privileged structure found in both natural products and synthetic compounds including small molecule drugs. We present the synthesis of a series of 13 new DE-amino acid conjugates which were screened for cancer cells antiproliferation activity. Structure-activity relationship suggests ester and phenyl groups in DE-Phe-OEt 4 c are important for the activity. Compound 4 c inhibited strongly MCF-7 3D tumor sphere formation and have favourable calculated physical chemical properties according to Lipinski's rule of 5. Docking study suggests estrogen receptor and/ or 3a-HSD type 3 protein could be the target(s) for anticancer activity of this class of compounds.