Eco-friendly and potential colin esterase enzyme inhibitor agent sulfonyl hydrazone series: Synthesis, Bioactivity Screening, DFT, ADME properties, and Molecular Docking study

Abstract

In this study, new compounds containing the sulfonamide group and having inhibitory activity on cholinesterase enzymes (AChE, BChE) were synthesized. For this purpose, three new sulfonylhydrazone compounds were synthesized from different alkylsulfonic acid hydrazide and N’-(4-diethylamino) salicylaldehyde and designed by the green chemistry method in shorter time and more environmentally friendly. The structures of the synthesized compounds were characterized by elemental analysis (CHNS), 1HNMR , 13CNMR , and FT-IR. The effects of the synthesized sulfonylhydrazone derivatives (4Dea-salesh, 4Dea-salpsh, 4Dea-salbsh) on acetylcholinesterase and butyrylcholinesterase enzymes were investigated. According to the results, all synthesized compounds showed inhibitory effect on AChE and BChE enzymes. In particular, 4Dea-salbsh exhibited the best activity with an IC50 value of 9.549±0.75 μM on AChE. The Molecules were optimized by B3LYP, HF, and M062X methods with 6–31++g(d,p) basis sets. Then, their activities against biological materials namely acetylcholinesterase (AChE) (PDB ID: 4M0E and 1OCE) and butyrylcholinesterase (BChE) (PDB ID: 5NN0 and 6R6V), were compared. Molecular docking studies were performed to evaluate the binding interactions between the compounds and the enzymes. Subsequently, ADME/T properties were investigated to test the drug properties.