Design, Docking, Synthesis and Biological Evaluation of Novel Nicotinohydrazone Derivatives as Potential Butyrylcholinesterase Enzyme Inhibitor

In this research, some new heterocyclic hydrazone compounds bearing an aryl sulfonate moiety (2 a–i) were facilely synthesized for the first time and elucidated by some spectroscopic techniques (FT‐IR, 1H‐ and 13C NMR). The inhibitory potentials of all synthesized molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase enzymes were investigated. Also, DPPH, ABTS and CUPRAC antioxidant activities of all molecules were examined. In BChE assay, it was determined that 2‐Formylphenyl 4‐chlorobenzenesulfonate (1 a) (IC50=10.45 μM), 5‐(diethylamino)‐2‐formylphenyl 4‐Chlorobenzenesulfonate (1 h) (IC50=10.12 μM), and 1‐((2‐Nicotinoylhydrazono)methyl)naphthalen‐2‐yl 4‐chlorobenzenesulfonate (2 i) (IC50=9.89 μM) were found to be more effective than the standard compound galanthamine and donepezil. In DPPH assay, 2‐((2‐Nicotinoylhydrazono)methyl)phenyl 4‐chlorobenzenesulfonate (2 a) (IC50=361.03 μM) and 5‐Methoxy‐2‐((2‐nicotinoylhydrazono)methyl)phenyl 4‐chlorobenzenesulfonate (2 e) (IC50=348.9 μM) indicated the highest antioxidant activities. On the other hand, the molecular electrostatic potential (MEP) maps of compounds 1 a, 1 h, 2 i and galanthamine molecules were investigated. The molecular docking study for BChE enzyme structure was found to be compatible with the experimental results and MEP maps. In this research, nine hydrazone compounds were synthesized for the first time and investigated for their inhibitory potentials on some enzymes. Also, their antioxidant activities were evaluated. It was determined that these molecules, showed significant activities against BChE. The molecular docking study for BChE was found to be compatible with the experimental results and MEP maps.