Benzenesulfonamide derivatives as potent acetylcholinesterase, α-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 α-glycosidase (α-GLY) enzymes were determined. For the AChE and α-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 µM, 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, α-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.

Communicated by Ramaswamy H. Sarma

Keywords:

• α-Glycosidase
• acetylcholinesterase
• glutathione S-transferase
• molecular docking
• sulfonamide derivatives

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Research Fund of Anadolu University under grant number 1610S681.