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

• Published in: Brazilian Journal of Pharmaceutical Sciences 2017-01, Vol.53 (1)
• Main Authors: Hussain, Ghulam, Abbasi, Muhammad Athar, Aziz-ur-Rehman, Siddiqui, Sabahat Zahra, Shah, Syed Adnan Ali, Ashraf, Muhammad, Qurat-ul-Ain, Ahmad, Irshad, Malik, Rabia, Lodhi, Muhammad Arif, Khan, Farman Ali, Shahid, Muhammad, Fatima, Hina
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Antimicrobial agents; Iodine; PHARMACOLOGY & PHARMACY; Piperazine derivatives/ hemolytic activity; Piperazine derivatives/antimicrobial activity; Piperazine derivatives/Cholinesterase assays; Piperazine derivatives/in silico
• ISSN: 1984-8250; 2175-9790; 1984-8250; 2175-9790
• 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.