Synthesis, Characterization and Biological Evaluation of New Furo[2,3-b] pyridine Derivative: Molecular Docking,
Menier Al-Anazi1, Mohammad M Ibrahim2, Abdullah Al-Fawwaz3
1Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Kingdom of Saudi Arabia.
Introduction:
Pyridine-based derivatives are well-known for their broad-spectrum therapeutic applications, particularly as antimicrobial and antioxidant agents. However, clinical utility is often hindered by poor aqueous solubility and limited bioavailability. This study aimed to synthesize and evaluate the biological activity, pharmacokinetic properties, and nanoparticle-based enhancement of a novel furo[2,3-b]pyridine derivative.
Methods:
Ethyl 3-amino-4-(4-methoxyphenyl)-6-(p-tolyl)furo[2,3-b]pyridine-2-carboxylate (compound 3) was synthesized and structurally characterized using NMR, FT-IR, MS, and UV-Vis spectroscopy. Molecular docking studies were conducted to assess binding interactions with methionyltRNA synthetase (PDB ID: 3KFL) and xanthine oxidoreductase (PDB ID: 1R4U). ADME parameters were predicted using SwissADME. To improve solubility, silver nanoparticles (AgNPs) were synthesized using Compound 3 and characterized via scanning electron microscopy (SEM). In vitro antimicrobial and antioxidant assays were performed to validate in silico findings.
Results:
Docking simulations revealed strong binding affinities of compound 3 to both target enzymes, supporting its potential antimicrobial and antioxidant roles. ADME analysis demonstrated a favorable pharmacokinetic profile, with high gastrointestinal absorption, acceptable bioavailability, and compliance with Lipinski and related drug-likeness rules, but consistently poor solubility predictions across multiple models. The synthesized AgNPs exhibited a size range of 44-64 nm and significantly enhanced the solubility and stability of compound 3. In vitro assays demonstrated that the AgNPs exhibited superior antimicrobial activity, particularly against Staphylococcus aureus and Bacillus subtilis, and a marked increase in antioxidant potential, achieving 64.62% radical scavenging activity compared to 16.49% for the free compound.
Discussion:
The integration of nanotechnology with pyridine-based pharmacophores effectively addressed the limitations of solubility and bioavailability. The enhanced biological efficacy of AgNPs underscores their potential as multifunctional therapeutic agents targeting microbial infections and oxidative stress.
Conclusion:
This study presents a promising nanoparticle-assisted strategy to enhance the therapeutic potential of pyridine-based compounds. The dual antimicrobial and antioxidant activities of furo[2,3- b]pyridine-based AgNPs offer a valuable platform for the deve.
