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.