Synthesis, biological screening and molecular docking studies of some ethylated sulfonamides having 1,4-Benzodioxane moiety
Irshad, M.; Abbasi, M.A.; Rehman, A.R.; Siddiqui, S.Z.; Ali, M.S.; Ashraf, M.; Ismail, T.; Ahmad, I.; Hassan, S.; Lodhi, M.A.; Jamal, S.B.
Pakistan Journal of Pharmaceutical Sciences 29(6): 1913-1925
2016
ISSN/ISBN: 1011-601X PMID: 28375106 Document Number: 688432
The presented study comprises the synthesis of a new series of ethylated sulfonamides in which 1,4-benzodioxane moiety has been incorporated. The reaction of 1,4-benzodioxane-6-amine (1) with ethane sulfonyl chloride (2) yielded N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethanesulfonamide (3), which further on treatment with various alkyl/aralkyl halides, 4a-r, in N,Nꞌ-dimethylformamide (DMF) and in the presence of lithium hydride (LiH) acting as a weak base and catalyst; yielded derivatives of N-alkyl/aralkyl substituted N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethanesulfonamides (5a-r). The characterization of these derivatives was carried out by different spectroscopic techniques like infra red, proton-NMR and mass spectrometry; then screened against various enzymes i.e. acetylcholinesterase, butyrylcholinesterase, lipoxygenase and α-glucosidase enzymes and five different bacterial strains. The synthesized compounds were found to be good inhibitors of lipoxygenase but moderate inhibitors of AChE, BChE and α-glucosidase; whereas compounds 3, 5a, 5f, 5n and 5r were found good antibacterial compounds. The interaction between inhibitors and target enzymes (cholinestrases and lipoxygenase) was computationally observed which correlated with the experimental results.