Sulfonamide derivatives of 2-amino-1-phenylethane as suitable cholinesterase inhibitors

Abstract

Purpose: To evaluate the enzyme inhibition activity of N-substituted sulfamoyl derivatives of 2-amino-1- phenylethane as probable new drug candidates for the treatment of Alzheimer's diseases. Methods: A series of sulfamoyl derivatives, 3a-l, of 1-amino-2-phenylethane (1) were synthesized by reacting with various aryl sulfonyl chlorides, 2a-l, in the presence of aqueous Na2CO3 solution under definite pH control. All the synthesized molecules were screened against three enzymes, acetyl cholinesterase (AChE), butyryl cholinesterase (BChE) and lipoxygenase (LOX). The synthesized derivatives were further characterized by infra-red spectroscopy (IR), nuclear magnetic resonance (1HNMR) and electron ionization-mass spectrometry (EI-MS) for structure elucidation. Results: Screening against acetyl cholinesterase (AChE), butyryl cholinesterase (BChE) and lipoxygenase (LOX) showed these molecules to be suitable inhibitors of cholinesterase enzymes, AChE and BChE, relative to eserine, the reference standard. The molecule, 3c, remained effective with 50% inhibitory concentration (IC50) value of 82.93 ± 0.15 μM (relative to eserine with IC50 value of 0.04 ± 0.0001 μM) against AChE; similarly 3d was active against BChE with IC50 value of 45.65 ± 0.48 μM compared to eserine with IC50 value of 0.85 ± 0.00 μM. The molecule, 3f, was inactive against all the three enzymes. Conclusion: Overall, the results indicate that these compounds are active against cholinesterase enzymes but less potent against lipoxygenase enzyme. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.