Synthesis of Schiff Bases 2-{[(4-Hydroxyphenyl) methylidene] amino} propanoic Acid, 4-[(Phenylimino)methyl] Phenol, and 4-{[(3-Chlorophenyl) methylidene] amino} Phenol and Molecular Docking Studies Against EGFR

Abstract

The implementation of green chemistry methods significantly reduces the amount of chemical waste. This study aimed to employ environmentally friendly techniques for synthesizing Schiff bases and evaluating their potential anticancer activity through molecular docking studies against EGFR. An innovative and sustainable condensation reaction was employed for the green synthesis of two Schiff bases, 4-[(phenylimino)methyl] phenol and 2-{[(4-hydroxyphenyl) methylidene] amino} propanoic acid, whereas the third Schiff base, 4-{[(3-chlorophenyl) methylidene] amino} phenol, was synthesized using a conventional reflux method involving p-aminophenol and 3-chlorobenzaldehyde. The product was purified by basic filtration, washed with water, and dried. The synthesized compounds were characterized by their physical properties, melting points, TLC, FTIR, and ¹H NMR spectroscopy. The first Schiff base was a pale-yellow solid with a melting point of 190-196∘C; Rf: 0.83 (n-pentane: ethyl acetate, 1:3); yield: 62.7%). The second Schiff base after synthesis showed a light pink colour and was a crystalline solid with a melting point of 118-123∘C (Rf: 0.66 (n-pentane: ethyl acetate, 1:3)); the yield was 42.1%. The third Schiff base was orange-yellow in colour, solid in nature, with a melting point of 106-110∘C; Rf: 0.72 (n-pentane: ethyl acetate) and a yield of 58.2%. Molecular docking analysis suggested favourable interactions with the EGFR receptor via conventional hydrogen bonding at Thr766, which was similar to native ligand interactions with the receptor. The Schiff base exhibited a binding affinity of −6.7 kcal/mol and an RMSD value of 1.814 Å, indicating an acceptable docking pose.