Synthesis, In Vitro Antimicrobial Activities, Molecular Docking, and ADMET Studies of Hydrazone‐Schiff Bases Bearing Ibuprofen Scaffold

Abstract In this research, we explore the synthesis and in vitro antibacterial activity of hydrazone Schiff base derivatives bearing ibuprofen nucleus. These derivatives were synthesized by treating ibuprofen with hydrazine hydrate in the presence of 1,1‐carbonyldiimidazole (CDI) in tetrahydrofuran (THF). The obtained hydrazide was further treated with various benzaldehydes in ethanol solvent containing acetic acid as a catalyst to get the desired hydrazone Schiff bases in good yields. Structures of these derivatives have been structurally deduced by means of modern spectroscopic techniques (FT‐IR, mass, 1 H‐NMR, and 13 C‐NMR) and screened against Gram‐positive andGram‐negative strains (ATCC) including Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC BAA‐1705), Staphylococos aureus (ATCC 33862), and Pseudomonas aeruginosa (ATCC 15442) and quiet diverse results were observed. All the compounds in the series presented significant levels of inhibition against all tested strains (MIC range 0.019 to 1.25 mg/mL). Most active compounds were reported as 2a (MIC 0.78 to 1.25 mg/mL) and 2d (0.019 to 1.25 g/mL). Molecular docking investigation was performed to know the binding interactions of the synthesized compounds with the targeted enzyme's active site.