Aktar_2026_Future.Med.Chem__1

AIMS: Cholinesterase inhibitors represent an important therapeutic strategy in combating Alzheimer's disease. MATERIAL AND METHODS: The novel 4-((2-(substitutedbenzoyl)hydrazinylidene)methyl)phenyl 2/3/4-(trifluoromethoxy)benzene-1-sulfonates (1-40) were synthesized from the reaction of 4-Formylphenyl-2/3/4-trifluoromethoxybenzene-1-sulfonate with various substituted benzoic acid hydrazides. The structures of all hybrid molecules were conclusively elucidated by elemental analysis and some spectroscopic techniques (IR, NMR, MS). These compounds were evaluated for their cholinesterase (AChE and BChE) inhibitory activities. RESULTS: Compound 33, carrying a nitro group at the 4-position of the phenyl ring among the series, exhibited the highest inhibitory activity, showing IC(50) values of 8.11 +/- 0.52 microM for AChE and 12.09 +/- 0.28 microM for BChE. The molecular docking studies elucidated the interactions of the active compounds with the actives sites of AChE and BChE enzymes were elucidated by molecular docking, supporting their observed anticholinesterase activity. CONCLUSION: The compatible results of experimental data and in silico analyses demonstrate that these compounds can be considered among effective and potential lead candidates for cholinesterase inhibition targeting AD.