Synthesis of new 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl) sulfonyl]amino}-N-(un/substituted-phenyl)acetamides as α-glucosidase and acetylcholinesterase inhibitors and their in silico study

Abstract

The aim of the present research work was to investigate the enzyme inhibitory potential of some new sulfonamides having benzodioxane and acetamide moieties. The synthesis was started by the reaction of N-2,3-dihydrobenzo[1,4]-dioxin-6-amine (1) with 4-methylbenzenesulfonyl chloride (2) in the presence of 10% aqueous Na 2 CO 3 to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-methylbenzenesulfonamide (3), which was then reacted with 2-bromo-N-(un/substituted-phenyl)acetamides (6a-l) in DMF and lithium hydride as a base to afford various 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl)sulfonyl] amino}-N-(un/substituted-phenyl)acetamides (7a-l). All the synthesized compounds were characterized by their IR and 1 H-NMR spectral data along with CHN analysis data. The enzyme inhibitory activities of these compounds were tested against a-glucosidase and acetylcholinesterase (AChE). Most of the compounds exhibited substantial inhibitory activity against yeast a-glucosidase and weak against AChE. The in silico molecular docking results were also consistent with in vitro enzyme inhibition data.

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

“…Similarly, these derivatives were proven more effective α-glucosidase inhibitors in comparison to the reported benzimidazoles [70], dihydropyrano[2,3-c]pyrazoles [71] and 2-thioxobenzo[g]quinazolines [72] but less potent than the sulfonamide chalcones [44]. Similarly, compounds 12i and 12k, the most potent derivatives of the series, having IC 50 values of 25.88 and 30.45 µM, respectively, were also found better α-glucosidase inhibitors compared to the recently reported N-arylacetamides [73]. These derivatives were found about 2.7-and 1.7-fold more potent enzyme inhibitors compared to the acarbose.…”