Bioactive sulfonyl hydrazones with alkyl derivative: Characterization, ADME properties, molecular docking studies and investigation of inhibition on choline esterase enzymes for the diagnosis of Alzheimer's disease

Abstract

In this work, new sulfonylhydrazone compounds with alkyl derivatives (SH1– SH4 series) were synthesized via a green chemistry method, and their inhibition effects on acetylcholinesterase and butyrylcholinesterase (AChE, BChE) were determined in vitro. This work was designed in two stages; in the first stage, using compounds that contain both sulfonamide and hydrazine groups which have important pharmacological properties, a series of sulfonyl hydrazone with alkyl derivatives (SH1– SH4) were synthesized with a method that is less time-consuming and more environmentalist that was by using different substitute groups containing aldehyde and ketone compounds. The structures of the synthesized compounds were characterized by elemental analyses, 1H NMR, 13C NMR, FT-IR methods. In the second stage, the effects of the synthesized sulfonyl hydrazones with alkyl derivatives on acetylcholinesterase and butyrylcholinesterase enzymes were examined. According to the results, all the synthesized compounds inhibited AChE and BChE enzymes. When the IC50 values were compared, SH2-3 (IC50 = 5.27 ± 0.05 μM) and SH3-3 (IC50 = 12.29 ± 1.47 μM) compounds which are containing the butyl group have the best inhibition effect on the AChE enzyme and BChE enzyme, respectively. In addition, the predictive properties of all compounds in terms of drug similarity were scanned using five Lipinski rules and ADME estimations. In silico ADME studies play an important role in improving and predicting drug compounds. In the ADME study; The absorption, distribution, metabolism, elimination, and properties of the molecules given below were theoretically calculated. Also, to evaluate the binding interactions between the sulfonylhydrazone compounds and enzymes, molecular docking studies were performed and the compounds with the best inhibition effect SH2-3 (for AChE enzyme) and SH3-3 (for BChE enzyme) were tested. Both in vitro and silico the results showed that two compounds could act as potent inhibitors of AChE, BChE.