Green mechanochemical synthesis of bis-imine derivatives: Multi-target docking, MD simulations, and in silico evaluation as potential antibacterial agents

HemanthKumar, Dharmapuri and Tokaji, György Marcell and R., Udaya Rajesh and Fiser, Béla and A., Singhal (2026) Green mechanochemical synthesis of bis-imine derivatives: Multi-target docking, MD simulations, and in silico evaluation as potential antibacterial agents. RESULTS IN CHEMISTRY, 29. No. 103762. ISSN 2211-7156

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Abstract

This study reports a green, solvent-free mechanochemical synthesis of novel bis-imine derivatives, offering a rapid and sustainable alternative to conventional thermal methods. The target compounds were obtained in 10 to 15 min via grinding, compared to 60 to 90 min under reflux. Although mechanochemical method yields (48–64%) were moderately lower than conventional yields (53–83%), the approach significantly reduces reaction time and eliminates the use of organic solvents. All the synthesized compounds were structurally characterized using 1H NMR, 13C NMR, HR-MS, FT-IR, and CHN analysis. Molecular docking against four bacterial targets (DNA Gyrase, Topoisomerase IV, Dihydropteroate Synthetase, and tRNA Synthetase) identified tRNA Synthetase and DNA Gyrase as the most promising ones based on docking scores. To further validate the stability of the protein-ligand interactions, 100 ns molecular dynamics (MD) simulations were performed on all the ligands in complexed with tRNA Synthetase and DNA Gyrase using GROMACS. Additional ADMET predictions have been done to describe toxicity and pharmacological properties of the synthesized bis-imines. This work combines synthetic and computational approaches to highlight the potential of mechanochemically synthesized bis-imines to identify promising candidates that may be useful for developing new antibacterial agents against resistant bacteria.

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