A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (7a–o) was developed as dual inhibitors of EGFR/
VEGFR-2. Compounds 7a–o were evaluated as antiproliferative agents with Erlotinib as the reference drug.
Results demonstrated that most of the tested compounds showed significant antiproliferative action with
GI50 values ranging from 28 to 104 nM, compared to Erlotinib (GI50 ¼ 33 nM), and compounds 7i–m were
the most potent. Compounds 7h, 7i, 7j, 7k, and 7l were evaluated as dual EGFR/VEGFR-2 inhibitors. These
in vitro experiments demonstrated that compounds 7j, 7k, and 7l are potent antiproliferative agents that
may operate as dual EGFR/VEGFR-2 inhibitors. Compounds 7j, 7k, and 7l were evaluated for their apoptotic
potential activity, where findings indicated that compounds 7j, 7k, and 7l promote apoptosis by activating
caspase-3, 8, and Bax and down-regulating the anti-apoptotic Bcl-2. Molecular docking simulations show
the binding mode of the most active antiproliferative compounds within EGFR and VEGFR-2 active sites.

A new class of benzimidazole-based derivatives (4a–j, 5, and 6) with potential dual
inhibition of EGFR and BRAFV600E has been developed. The newly synthesized compounds were
submitted for testing for antiproliferative activity against the NCI-60 cell line. All newly synthesized
compounds 4a–j, 5, and 6 were selected for testing against a panel of sixty cancer cell lines at a single
concentration of 10 μM. Some compounds tested demonstrated remarkable antiproliferative activity
against the cell lines tested. Compounds 4c, 4e, and 4g were chosen for five-dose testing against
60 human tumor cell lines. Compound 4c demonstrated strong selectivity against the leukemia
subpanel, with a selectivity ratio of 5.96 at the GI50 level. The most effective in vitro anti-cancer
assay derivatives (4c, 4d, 4e, 4g, and 4h) were tested for EGFR and BRAFV600E inhibition as potential
targets for antiproliferative action. The results revealed that compounds 4c and 4e have significant
antiproliferative activity as dual EGFR/BRAFV600E inhibitors. Compounds 4c and 4e induced
apoptosis by increasing caspase-3, caspase-8, and Bax levels while decreasing the anti-apoptotic Bcl2
protein. Moreover, molecular docking studies confirmed the potential of compounds 4c and 4e to act
as dual EGFR/BRAFV600E inhibitors