Synthesis, molecular docking, ADMET profiling, and anti-PC3 activity of new Schiff base derivatives

Abstract

Schiff bases are significant compounds that occur naturally or can be synthesized in laboratory settings. In this study, we synthesized three novel Schiff bases, designated as compounds 1 to 4, specifically 4-{(E)-[4-(chloromethyl) phenyl] diazenyl}-2-{[(4-substituted phenyl)imino]-methyl}phenol. The synthesis involved the reaction of 5-{(E)-[4-(chloromethyl) phenyl] diazenyl}-2-hydroxybenzaldehyde with various 4-substituted anilines, including 4-ethyl, 4-bromo, and 4-propoxy aniline. The synthesized compounds were characterized using FTIR spectroscopy and ¹H NMR spectroscopy. To evaluate their biological activity, we employed the diffusion method to test the antibacterial efficacy of these compounds against several bacterial strains, namely Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Among the derivatives tested, derivative 2 exhibited the highest inhibition zone, indicating its potent antibacterial activity. In addition to their antibacterial properties, derivative 3 was assessed for its anti-cancer effects against the PC3 prostate cancer cell line. The results demonstrated a significant reduction in cell viability over time, with an IC₅₀ value of 26.17 μg/mL after 48 h compared to 52.33 μg/mL after 24 h. This suggests that derivative 3 becomes increasingly effective in inhibiting cancer cell proliferation over extended exposure. Furthermore, Schiff bases 1 and 3 were investigated for their ability to inhibit α-amylase derived from the blood of pancreatic cancer patients. Among these, derivative 3 was the most effective, achieving a 39.3 % inhibition at a concentration of 75 μg/mL, highlighting its potential as a therapeutic agent in managing pancreatic cancer. To gain insights into the molecular interactions of the synthesized compounds, docking analysis was performed. Moreover, the synthesized compounds were evaluated against specific bacterial strains using the PDB ID 4URO, further confirming their potential as effective antibacterial agents. In silico ADMET analysis was also conducted to assess the pharmacokinetic properties of the synthesized molecules.