Synthesis, Spectroscopic Characterization and Computational Investigations (DFT, Docking, Molecular Dynamics, MM/PBSA) of New Benzylidene-amino-propan-2-ol Derivatives

In this study, novel Schiff base derivatives were synthesized through the condensation reactions of aldehyde and amine-functionalized precursors. The structures of the synthesized compounds were confirmed using Fourier Transform Infrared (FT-IR), proton and carbon Nuclear Magnetic Resonance (1H‑NMR and 13C-NMR) spectroscopies. Density Functional Theory (DFT) calculations at the 6‑311++G(d,p) level were performed to support the molecular structures. Schiff bases are well-known for their broad biological activity profiles, and their structural diversity makes them promising scaffolds for developing new agents against rising antimicrobial and antiparasitic drug resistance. Considering the urgent need for novel therapeutics due to the rapid development of resistance among pathogenic microorganisms, the antibacterial and leishmanicidal activities of three synthesized Schiff base derivatives were evaluated by the microdilution method. The results demonstrated that compound 2a shows significant activity and may be a potential drug candidate against both bacteria and Leishmania. Further in vitro and in vivo studies are important to validate its therapeutic potential. Trypanothione reductase (TR), a key redox enzyme in Leishmania infantum, was selected as a validated drug target, and compound 2a was examined using molecular docking and 100 ns molecular dynamics (MD) simulations. The TR–2a complex exhibited stable structural behavior with low Root Mean Square Deviation (RMSD), consistent Radius of Gyration (Rg), and stable Solvent Accessible Surface Area (SASA) values. Transient hydrogen bonds and a favorable MM/PBSA binding energy (–27.31 kcal/mol) supported strong ligand affinity. Overall, the combined biological and computational findings reveal that these Schiff base derivatives particularly compound 2a show promise as lead candidates for future antiparasitic drug development.