New synthetic chitosan Schiff bases bearing pyranoquinolinone or benzonaphthyridine and their silver nanoparticles derivatives with potential activity as antioxidant and molecular docking study for EGFR inhibitors

• Published in: RSC advances 2024-09, Vol.14 (41), p.29919-29933
• Main Authors: Hassan, Shrouk M, Morsy, Jehan M, Hassanin, Hany M, Othman, Elham S, Mostafa, Mai A
• Format: Article
• Language: English
• Subjects: Antioxidants; Chemical synthesis; Chitosan; Diketones; Growth factors; Imines; Kinases; Molecular docking; Nanoparticles; NMR; Nuclear magnetic resonance; Radicals; Receptors; Silver; Tyrosine
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d4ra05117c

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, 1 H NMR, 13 C 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, CS 1 and CS 2 . The new chitosan Schiff bases were grafted on silver nanoparticles, providing CS 1 /Ag and CS 2 /Ag structures. However, CS 1 and CS 2 and their silver nanoparticles were characterized by FT-IR, XRD, SEM-EDX, XRF, TEM, TGA, and DSC. The target compounds CS 1 , CS 2 , CS 1 /Ag , and CS 2 /Ag were assessed as radical scavengers against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH%). The results showed that CS 1 and CS 2 had a better ability to scavenge DPPH radical than its unmodified chitosan. CS 1 /Ag and CS 2 /Ag , combining the unique properties of silver and Schiff bases, displayed excellent antioxidant activity (IC 50 , 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 CS 1 /Ag displayed potent inhibitory activity towards EGFR with IC 50 20.45 μg mL −1 compared to reference drug sorafenib (IC 50 = 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 CS 1 has a higher binding energy than CS 2 and CS regarding EGFR kinase, which agreed with the results obtained from the experimental EGFR inhibition assay. Two chitosan-based Schiff bases, CS 1 and CS 2 were synthesized, and they were grafted onto silver nanoparticles, creating CS 1 /Ag and CS 2 /Ag structures. They were assessed as antioxidant and EGFR inhibitors.