In this study, two new carboxaldehydes 3, and 4 were synthesized by Vilsmeier-Haack formylation of 6-butyl-benzo[h][1,6]naphthyridine-2,5-dione 2 and 6-butyl-pyrano[3,2-c]quinolinone 1, respectively. Structures of newly synthesized compounds were achieved by IR, 1H NMR, 13C NMR, mass techniques, and elemental analyses. The two synthesized carboxaldehydes 3 and 4 were used as precursors for the synthesis of two new chitosan-based Schiff bases, CS1 and CS2. The new chitosan Schiff bases were grafted on silver nanoparticles, providing CS1/Ag and CS2/Ag structures. However, CS1 and CS2 and their silver nanoparticles were characterized by FT-IR, XRD, SEM-EDX, XRF, TEM, TGA, and DSC. The target compounds CS1, CS2, CS1/Ag, and CS2/Ag were assessed as radical scavengers against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH%). The results showed that CS1 and CS2 had a better ability to scavenge DPPH radical than its unmodified chitosan. CS1/Ag and CS2/Ag, combining the unique properties of silver and Schiff bases, displayed excellent antioxidant activity (IC50, 59.13, and 32.54 μg mL-1, respectively). In addition, the previous compounds were tested in vitro for inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase using the EGFR kinase assay kit (Cat. #40321). In particular, compound CS1/Ag displayed potent inhibitory activity towards EGFR with IC50 20.45 μg mL-1 compared to reference drug sorafenib (IC50 = 0.76 μg mL-1). The bioactivity of new chitosan Schiff bases was studied by molecular docking to see how they bind with the EGFR receptor. The results implied that CS1 has a higher binding energy than CS2 and CS regarding EGFR kinase, which agreed with the results obtained from the experimental EGFR inhibition assay.
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