Therapeutic potential of sulfonate-based hydrazide hydrazones in neurodegenerative diseases: SAR insights and molecular modeling studies.

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 IC50 values of 8.11 ± 0.52 µM for AChE and 12.09 ± 0.28 µM 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.