Synthesis of Vanillin derivative Schiff's bases from threonine, and valine: Structural study and multiscale computational modeling.

Addressing the escalating global challenge of antimicrobial resistance, this study reports the synthesis, comprehensive structural characterization, and multiscale computational modeling of two novel vanillin-derived Schiff's bases, 1 (from threonine) and 2 (from valine). Spectral analyses confirmed their successful formation. Antimicrobial assays revealed significant activity against a panel of Gram-negative (Escherichia coli, Pseudomonas aeruginosa), Gram-positive (Bacillus subtilis, Staphylococcus aureus), and fungal (Candida albicans, Aspergillus flaves) strains. Notably, compound 1 exhibited potent inhibition against B. subtilis (18 mm zone), while compound 2 demonstrated superior broad-spectrum efficacy, with inhibition zones of 20 mm against P. aeruginosa and 19.6 mm against S. aureus, often surpassing respective control antibiotics (amikacin: 17-18 mm, nystatin: 16-18 mm). Computational investigations, including Natural Bonding Orbital (NBO) and Non-Covalent Interactions (NCI) analyses, elucidated intramolecular stabilization and reactivity profiles. Drug-likeness and pharmacokinetic evaluations (SwissADME) indicated favorable solubility, high gastrointestinal absorption, and synthetic accessibility. Insights into tautomeric equilibria (SwissParam) and potential biological targets (SwissTargetPrediction), such as proteases and lyases, underscore their therapeutic relevance. This integrated experimental and theoretical approach highlights the promising potential of these novel Schiff's bases as effective antimicrobial agents, providing a robust foundation for future drug development efforts.