Design, Synthesis, In Vitro and Molecular Docking Evaluation of Triphenylphosphonium‐Hydrazone Hybrids Against MDR Bacteria, AChE, and Laryngeal Cancer (Hep‐2)

ABSTRACT This study reports the synthesis of Triphenylphosphonium–Hydrazone hybrid organic salts, their characterization by FTIR, NMR, and HR‐MS, and evaluation of their biological activities. The compounds were tested for acetylcholinesterase (AChE) inhibition, anticancer activity against Hep‐2 cells, antibacterial effects against Staphylococcus aureus (S. aureus), Enterococcus faecalis (E. faecalis), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli ( E. coli), methicillin‐resistant S. aureus (MRSA), and multidrug‐resistant E. coli (MDR E. coli), as well as antibiofilm activity against resistant strains. Although weak anticancer effects were observed, compound 6 demonstrated the most significant activity. At 0.1 mg/mL, it inhibited AChE by 84%. This compound also exhibited strong antibacterial potency, with minimum inhibitory concentration (MIC) values of 4 µg/mL for S. aureus , 2 µg/mL for E. faecalis , 16 µg/mL for E. coli , 8 µg/mL for MRSA, and 128 µg/mL for both P. aeruginosa and MDR E. coli . Furthermore, compound 6 showed potent antibiofilm activity against MRSA and MDR E. coli . In silico molecular docking supported these findings, revealing favorable binding affinities with bacterial proteins and AChE, with the lowest score observed for MDR E. coli (–7.525 kcal/mol). Collectively, these results suggest that compound 6 represents a promising multifunctional lead with antibacterial, antibiofilm, and AChE inhibitory properties, warranting further mechanistic and in vivo investigation.