Synthesis of Arylsulfonyl Hydrazone Derivatives: Antioxidant Activity, Acetylcholinesterase Inhibition Properties, and Molecular Docking Study
Yasin Demirci, Erbay Kalay, Yakup Kara, Halil İbrahim Güler, Zehra Can, Engin Şahin
Abstract
Abstract In this current paper, fifteen novel sulfonyl hydrazone derivatives have been successfully synthesized and evaluated for antioxidant activity as well as their effects on inhibitory activity toward acetylcholinesterase (AChE). By using 1 H NMR, 13 C NMR, FT‐IR, and high‐resolution mass spectrometry methods, the full characterization data of the novel compounds were obtained. The synthesized compounds capacity to inhibition glucosidase and exhibit antioxidant activity were tested in vitro . It was determined that compounds ( E )‐4‐((2‐((4‐chlorophenyl)sulfonyl)hydrazone)methyl)‐2‐methoxyphenylfuran‐2‐carboxylate ( 21 ), ( E )‐2‐methoxy‐4‐((2‐(phenylsulfonyl)hydrazone)methyl)phenylfuran‐2‐carboxylate ( 17 ) and ( E )‐4‐((2‐((4‐bromophenyl)sulfonyl)hydrazone)methyl)‐2‐methoxyphenylfuran‐2‐carboxylate ( 25 ) showed good antioxidant activity. Upon examining the acetylcholinesterase inhibitory activity, it was determined that compounds (E) ‐2‐methoxy‐4‐((2‐((4‐methoxyphenyl)sulfonyl) hydrazone)methyl)phenylacetate ( 27 ) (10.39 μM), ( E )‐4‐((2‐((4‐chloro phenyl)sulfonyl) hydrazone)methyl)‐2‐methoxyphenylfuran‐2‐carboxylate ( 21 ) (10.81 μM), ( E )‐4‐((2‐((4‐chloro phenyl)sulfonyl)hydrazone)methyl)‐2‐methoxyphenyl thiophene‐2‐carboxylate ( 22 ) (12.92 μM) and ( E )‐2‐methoxy‐4‐((2‐(phenylsulfonyl)hydrazone)methyl)phenylfuran‐2‐carboxylate ( 17 ) (12.93 μM) showed potent inhibitory effects. Molecular docking simulations were used to investigate the interactions of novel sulfonyl hydrazone derivatives with human acetylcholinesterase protein. The ligands exhibited strong binding to the receptor protein with potent inhibition.