Benzenesulfonamide derivatives as potent acetylcholinesterase, alpha-glycosidase, and glutathione S-transferase inhibitors: biological evaluation and molecular docking studies

Abstract

Sulfonamide derivatives exhibit a wide biological activity and can function as potential medical molecules in the development of a drug. Studies have reported that the compounds have an effect on many enzymes. In this study, the derivatives of amine sulfonamide (1i-11i) were prepared with reduced imine compounds (1-11) with NaBH4 in methanol. The synthesized compounds were fully characterized by spectral data and analytical. The effect of the synthesized derivatives on acetylcholinesterase (AChE), glutathione S-transferase (GST) and a-glycosidase (alpha-GLY) enzymes were determined. For the AChE and alpha-GLY, the most powerful inhibition was observed on 10 and 10i series with K-I value in the range 2.26 +/- 0.45-3.57 +/- 0.97 and 95.73 +/- 13.67-102.45 +/- 11.72 mu M, respectively. K-I values of the series for GST were found in the range of 22.76 +/- 1.23-49.29 +/- 4.49. Finally, the compounds have a stronger inhibitor in lower concentrations by the attachment of functional electronegative groups such as two halogens (-Br and -CI), -OH to the benzene ring and -SO2NH2. The crystal structures of AChE, alpha-GLY, and GST in complex with selected derivatives 4 and 10 show the importance of the functional moieties in the binding modes within the receptors.