Pharmacological Evaluation and Synthesis of New Sulfonamides Derivatives Based on 1,4-Benzodioxane

Abstract

We report here the synthesis of a series of N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide and its N-substituted derivatives with benzyl chloride and ethyl iodide. Initially, 2,3-dihydrobenzo[1,4]dioxine-6-sulfonyl chloride (1) was subjected to react with various aryl amines (2a-e) to afford parent compounds N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (3a-e). At second step, these parent compounds were reacted with benzyl chloride (4) and ethyl iodide (5) as to synthesize N-benzyl-N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (6a-e) and N-ethyl-N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (7a-e) in the presence of lithium hydride and N,Nꞌ-dimethylformamide respectively. FT-IR, Nuclear Magnetic Resonance (1H-NMR) and Mass Spectrometry (MS) techniques were used to investigate the structures of these synthesized compounds. A fingerprinted study was conducted against some enzymes like butyrylcholin-esterase (BChE), acetylcholinesterase (AChE) and lipoxygenase (LOX). This study revealed that most of them demonstrated a moderate activity against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) however promisingly a good activity against lipoxygenase enzyme was observed. Finally, an antimicrobial and hemolytic activities of these sulfonamides were probed which confirmed that the parent sulfonamides 3b have the proficient antimicrobial activities, while the derivatives 6a, 7a, 7b and 7c explored a good activity against the selected panel of bacterial and fungal species. All the compounds were further computationally docked against (LOX), (BChE) and (AChE) enzymes and these interaction highlighted the importance of sulfonamides in the inhibition of the target enzymes.

Keywords

• 2
• 3-dihydrobenzo[1
• 4]dioxine-6-sulfonyl chloride
• Lipoxygenase enzyme
• 1H-NMR
• EI-MS
• Antimicrobial and hemolytic activities