Synthesis, characterization, and biological evaluation of new quinazolin-4-one derivatives hybridized with pyridine or pyran moiety

摘要

A new series of 2-(furan-2-yl)-4-oxoquinazolin-3-phenyl derivatives hybridized with pyridine 3a-d, 4a-d or pyran moiety 5a-d were synthesized; their structures were confirmed by spectral and elemental analysis. Cytotoxicity was evaluated on three cancer cell lines (HEPG2, HCT116 and MCF7) using the sulphorodamine-B assay method and doxorubicin as a reference drug. Compound 5d showed a closely similar activity to doxorubicin on MCF7; their IC50 values are 4.6 and 4.4 nmol/mL, respectively. In addition, compounds 4b and 4c exhibited a closely similar activity to doxorubicin on HEPG2 cancer cells; their IC50 values expressed in nmol/mL are 6.6, 6.7, and 5.7, respectively. Moreover, compound 4b (IC50 = 1.2 nmol/mL) was four times more potent than doxorubicin (IC50 = 4.8 nmol/mL) on HCT116, and compound 5d (IC50 = 0.2 nmol/mL) revealed potency equal to 24 times the potency of doxorubicin on the same cancer cell line. The most active compounds were screened against EGFR TK, and results showed that compound 5d was the most potent inhibitor; its percentage of inhibition was 95.6. Furthermore, compound 5d was docked into the EGFR binding site to explore its possible interactions with EGFR TK.