Coumarin–furo[2,3-d]pyrimidone hybrid molecules targeting human liver cancer cells: synthesis, anticancer effect, EGFR inhibition and molecular docking studies†

Abstract

The design, synthesis and investigation of antitumor activities of some coumarin–furo[2,3-d]pyrimidone hybrid molecules are reported. In vitro, HepG2 cells were used to investigate the cytotoxicity of 6a–n and 10a–n. The results demonstrated that coupling a furopyrimidone scaffold with coumarin through a hydrazide linker can effectively improve their synergistic anticancer activity. The coumarin–furo[2,3-d]pyrimidone combination 10a exhibited significant inhibitory activity against HepG2 cells with IC₅₀ = 7.72 ± 1.56 μM, which is better than those of gefitinib and sorafenib. It is worth mentioning that the coumarin–furo[2,3-d]pyrimidone combination 10a showed excellent inhibition of the EGFR enzymatic activity with IC₅₀ = 1.53 μM and 90% inhibition at 10 μM concentration. In silico investigation predicts the possibility of direct binding between the new coumarin–furo[2,3-d]pyrimidone hybrid molecules and the EGFR. The results suggest that coumarin–furo[2,3-d]pyrimidone hybrid molecules are potential antitumor agents targeting human liver cancer cells.