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

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.

Automated summary

Sulfonamide derivatives have a wide range of biological activities and potential as medical molecules in drug development. Studies have shown that these compounds have an impact on various enzymes. The synthesized derivatives demonstrate inhibitory effects on AChE, GST, and α-GLY enzymes, with stronger inhibition observed at lower concentrations through the addition of functional electronegative groups.