Acetamide Derivatives of N-Methyl-4- Hydroxyaniliniumsulfate: Design, Synthesis, Spectral Characterization and in silico Study to Report them as Therapeutic Agents

The compounds bearing sulfamoyl and acetamoyl groups have been found to show various biological
activities. In the present research work, a series of O- and N-substituted derivatives were synthesized,
starting with planetol (1). First N-methyl-4-hydroxyanilinium sulfate (1; planetol or metol) was treated
with different aryl sulfonyl chlorides (2a-j) using aq. sodium carbonate solution as reaction medium to
yield N-substituted derivatives, 3a-j. The electrophile, N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-
bromoacetamide (5) was prepared by the reaction of 2,3-dihydro-1,4-benzodioxin-6-amine (4) and 2-
bromoacetylbromide in a weak basic aqueous medium. The target O-substituted molecules, 6a-j,
were synthesized by gearing up the electrophile, 5, with the molecules, 3a-j, in a polar aprotic solvent
using LiH as activator. The proposed structures of all the synthesized molecules were corroborated by
IR, 1H-NMR and EIMS spectral data. The in vitro enzyme inhibition and antibacterial studies rendered
the synthesized molecules as better cholinesterase inhibitors and moderately better antibacterial
agents. To explore the binding modes of the synthesized compounds, all of them were
computationally docked against the active sites of acetyl cholinesterase (AChE), butyryl
cholinesterase (BChE) and lipoxygenase (LOX). The compounds showed significant interactions and
good correlation with the experimental data.