Design, Docking, Synthesis and Biological Evaluation of Novel Nicotinohydrazone Derivatives as Potential Butyrylcholinesterase Enzyme Inhibitor
Yusuf İslam Esmer, Ercan Çınar, Eyüp Başaran
Abstract
Abstract 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, 1 H‐ and 13 C 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) (IC 50 =10.45 μM), 5‐(diethylamino)‐2‐formylphenyl 4‐Chlorobenzenesulfonate ( 1 h ) (IC 50 =10.12 μM), and 1‐((2‐Nicotinoylhydrazono)methyl)naphthalen‐2‐yl 4‐chlorobenzenesulfonate ( 2 i ) (IC 50 =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 ) (IC 50 =361.03 μM) and 5‐Methoxy‐2‐((2‐nicotinoylhydrazono)methyl)phenyl 4‐chlorobenzenesulfonate ( 2 e) (IC 50 =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.