Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

• Main Authors: Abbasi, M.A (Author), Ahmad, I. (Author), Ashraf, M. (Author), Aziz-ur-Rehman (Author), Fatima, H. (Author), Hussain, G. (Author), Khan, F.A (Author), Lodhi, M.A (Author), Malik, R. (Author), Qurat-ul-Ain (Author), Shah, S.A.A (Author), Shahid, M. (Author), Siddiqui, S.Z (Author)
• Format: Article
• Language: English
• Published: Faculdade de Ciencias Farmaceuticas (Biblioteca) 2017
• Subjects: [4 [4 [(3,5 dimethyl 4 morpholinyl)sulfonyl]benzyl] 1 piperazinyl](2 furyl)methanone; 2 furyl [4 [4 (1 piperidinylsulfonyl)benzyl] 1 piperazinyl]methanone; 2 furyl [4 [4 (4 morpholinylsulfonyl)benzyl] 1 piperazinyl]methanone; 2 furyl [4 [4 [(2 methyl 1 piperidinyl)sulfonyl]benzyl] 1 piperazinyl]methanone; 2 furyl [4 [4 [(2,6 dimethyl 1 piperidinyl)sulfonyl]benzyl] 1 piperazinyl] 2 methanone; 2 furyl [4 [4 [(3 methyl 1 piperidinyl)sulfonyl]benzyl] 1 piperazinyl]methanone; 2 furyl [4 [4 [(3,5 dimethyl 1 piperidinyl)sulfonyl]benzyl] 1 piperazinyl]methanone; 2 furyl [4 [4 [(4 methyl 1 piperidinyl)sulfonyl]benzyl] 1 piperazinyl]methanone; acetylcholinesterase; antibacterial activity; antiinfective agent; Article; Bacillus subtilis; cholinesterase; controlled study; cytotoxicity test; drug determination; drug structure; drug synthesis; electrospray mass spectrometry; enzyme activity; Escherichia coli; IC50; infrared spectroscopy; methanone derivative; molecular docking; nonhuman; physostigmine; Piperazine derivatives/ hemolytic activity; Piperazine derivatives/antimicrobial activity; Piperazine derivatives/Cholinesterase assays; Piperazine derivatives/in silico; proton nuclear magnetic resonance; Salmonella enterica serovar Typhi; Staphylococcus aureus; unclassified drug
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 19848250 (ISSN)
• ISSN: 19848250 (ISSN)
• DOI: 10.1590/s2175-97902017000115237

In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 µM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 µM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents. © 2017, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.