Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAF V600E : Design, Synthesis, and Antiproliferative Activity.

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF V600E . These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8 , 9 , 18 , and 19 inhibited cell proliferation significantly in the four cancer cells, with GI 50 values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI 50 = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF V600E . Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAF V600E . Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.