Bench and Byte: Synthesis, DFT, ADMET, and Molecular Docking on a Pair of Antibacterial Schiff Bases Targeting DNA Gyrase

ABSTRACT Schiff bases are privileged azomethine pharmacophores with diverse bioactivity. In this report, two new hydrazine‐derived Schiff bases, L 1 and L 2, were synthesized. The structures were confirmed by experimental approaches involving IR, UV–vis, 1 H, and 1 3 C NMR spectroscopy and showed strong correlation with theoretical computational predictions. Molecular reactivity was explored using DFT (B3LYP/6‐311G(d,p), SMD/water) through frontier orbitals, electrostatic potential, and global reactivity descriptors. Antibacterial evaluation against Escherichia coli , Staphylococcus aureus , and Pseudomonas aeruginosa showed strain‐selective potency: L 1 was most active against S. aureus and E. coli (MIC 4.9 and 6.5 µg/mL), while L 2 displayed moderate activity against P. aeruginosa (MIC 8.4 µg/mL). Ciprofloxacin remained the strongest reference (MIC 0.049–0.521 µg/mL). Docking with DNA gyrase (PDB ID 6F86) indicated favorable binding for L 1 (−6.4 kcal/mol) and L 2 (−6.0 kcal/mol) vs. ciprofloxacin (−7.0 kcal/mol). ADMET predictions supported acceptable drug‐likeness and low toxicity. These results highlight hydrazine‐based Schiff bases as promising leads for antibacterial design against multidrug resistance.