Compound(Sailong)

Derivatives 2-11 were evaluated for cytotoxicity against the human lung (A549), breast (MCF-7), colorectal (HCT-116) and hepatocellular (HepG2) cancer cell lines. The compounds were also evaluated through enzymatic assays as dual mutated epidermal growth factor receptor (EGFR^T790M) and vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. Cytotoxic effects on A549 cell lines, compared to sorafenib (4.04 μM) and erlotinib (5.49 μM), showed that compounds 4, 5, 6, 7, 8, 10 and 11 with the IC₅₀ values of 5.50-8.00 μM exhibited very high activities. Cytotoxicity on MCF-7 cell lines, compared to sorafenib (5.58 μM) and erlotinib (8.20 μM), showed that compounds 5, 6 and 7 established very high activities with the IC₅₀ values of 7.55, 6.95 and 5.60 μM, respectively. Cytotoxicity on HCT-116, compared to sorafenib (5.05 μM) and erlotinib (13.91 μM), showed that compound 7 with the IC₅₀ value of 9.50 μM, showed very good cytotoxicity. Compounds 5, 6, 7, 8 and 10 exhibited very high cytotoxic activities against HepG2 cell line with the IC₅₀ values in the range 8.00-9.65 μM, compared to sorafenib (4.00 μM) and erlotinib (7.73 μM). Moreover, the estimated structures 3, 4, 5, 6, 7, 8 and 10 indicated low toxicity on VERO cells with the IC₅₀ values of 48.80-52.50 μM. Furthermore, compounds 7, 6, 5 and 10 showed very good VEGFR-2 inhibitions at IC₅₀ = 0.96, 1.10, 1.35 and 1.90 μM, respectively. As well, Structures 10, 7 and 6 highly inhibit EGFR^T790M at IC₅₀ = 0.30, 0.35 and 0.40 μM respectively. Molecular docking was carried out for all derivatives to show their binding affinities and orientations inside the active sites of VEGFR-2 and EGFR^T790M receptors to support the in vitro results. The data obtained from docking is highly matched with that obtained from biological testing.