Synthesis, Characterization and Biological Screening of N-Substituted (5-Chloro-2-methoxyphenyl)benzene Sulfonamide

Abstract

In the present study, a series of N-substituted (5-chloro-2-methoxyphenyl)benzene sulfonamide have been synthesized. The reaction of benzene sulfonyl chloride (1) with 2-amino-4-chloroanisole (2) yielded N-(5-chloro-2-methoxyphenyl)benzene sulfonamide (3). Finally the target compounds (5a-k) were obtained by stirring N-(5-chloro-2-methoxyphenyl)benzene sulfonamide with different electrophiles (4a-k) in the presence of N,N-dimethyl formamide and sodium hydride. The structures of the synthesized compounds were established by spectroscopic techniques like ¹H NMR and EI-MS. These compounds were assayed for their antioxidant activities by using 2,2-diphenyl-1-picrylhydrazil (DPPH) scavenging and other biological activities via screening them against acetylcholinesterase, butyrylcholinesterase and lipoxygenase enzymes, however, these showed prominent activity against acetylcholinesterase enzyme. It is clearly evident from the results that the compounds N-methyl-(5-chloro-2-methoxyphenyl)benzene sulfonamide (5a), N-allyl-N-(5-chloro-2-methoxyphenyl)benzene sulfonamide (5e) and N-2"-phenylethyl-N-(5-chloro-2-methoxyphenyl)benzene sulfonamide (5j) were found to be promising inhibitors against acetylcholinesterase enzyme having IC₅₀ value of 34.61 ± 0.62, 40.21 ± 0.25 and 45.11 ± 0.22 μmol/L, respectively, relative to Eserine, a reference standard with IC₅₀ value of 0.04 ± 0.001 μmol/L.