Design and synthesis of some new imidazole-morpholine-1,2,4-oxadiazole hybrids as EGFR targeting in vitro anti-breast cancer agents

Abstract

Herein, we synthesized some new imidazole-moprholine-1,2,4-oxadiazoles (7a-7o) and characterized their structures using 1H NMR, 13C NMR, ESI-mass and CHN analyses techniques. All the compounds were further evaluated for their in vitro anti-proliferative activity against three human breast cancer cell lines like MCF-7, MDA-MB-231 and MDA-MB-468 and results revealed that compound 7b showed greater activity against three breast cancer cells than the standard drug 5-Fluorouracil (5-FU) with IC50 values <10 μM. As well, compounds 7e, 7j and 7m displayed greater activity against MCF-7 than the 5-FU with IC50 values in the range of 7.1–10.2 μM. Further, the in vitro tyrosine kinase epidermal growth factor receptor (EGFR) activity revealed that compound 7b exhibited comparable (IC50 = 0.47 μM) activity against EGFR with the standard drug Erlotinib (IC50 = 0.43 μM). Finally, in silico molecular docking studies showed important binding interactions of most potent compounds 7b, 7e, 7j and 7m with the EGFR (pdb id 4HJO) and these compounds have encouraging binding energies and inhibition constants as compared to Erlotinib.