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
• Main Author: Hussain G.; Abbasi M.A.; Aziz-ur-Rehman; Siddiqui S.Z.; Shah S.A.A.; Ashraf M.; Qurat-ul-Ain; Ahmad I.; Malik R.; Lodhi M.A.; Khan F.A.; Shahid M.; Fatima H.
• Format: Article
• Language: English
• Published: Faculdade de Ciencias Farmaceuticas (Biblioteca) 2017
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018664413&doi=10.1590%2fs2175-97902017000115237&partnerID=40&md5=026c95a5757de64b42aa338b0846c966

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.