Novel (Z)-3-(2-(quinazolin-4-yloxy)phenyl)acrylates as potential EGFR inhibitors deriving from the renovation of coumarin skeletons: Design, synthesis, characterization and antineoplastic activity.

The inhibitors of epidermal growth factor receptor (EGFR) have emerged as one of fastest-growing medications that are widely utilized to control the spread and proliferation of malignant tumors. Based on the structural features of quinazoline-containing EGFR inhibitors, a series of coumarin-deriving (Z)-3-(2-(quinazolin-4-yloxy)phenyl)acrylates as potential EGFR inhibitors were firstly constructed and evaluated for their antiproliferative effects against human pancreatic (PANC-1), gastric (SGC7901), hepatocellular (HepG2), breast (MDA-MB-231) and cervical (Hela) carcinoma cells. Strikingly, the IC50 values of a target molecule 5x against SGC7901 and MDA-MB-231 cells were respectively evaluated as 12.82 and 9.97 μM, which were slightly superior to that of fluorouracil (21.23 and 10.67 μM). Concurrently, the further investigations indicated that constructed (Z)-3-(2-(quinazolin-4-yloxy)phenyl)acrylates could evidently effect the colony formation, migration, invasion and adhesion of tumour cells in a dose-dependent manner. Subsequently, the feasibility of constructed (Z)-3-(2-(quinazolin-4-yloxy)phenyl)acrylates as potential EGFR inhibitors was ascertained by the relative surveys on molecular docking and molecular dynamics simulation analyses. This present work provided a necessary replenishment for the structural optimizations of quinazoline-containing EGFR inhibitors.