2-Furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer's diseases: In vitro and in silico studies

Abstract

The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (1; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound 1 with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) in a basic, polar and protic medium to obtain the parent sulfonamide 3 which was then treated with different electrophiles, 4a-g, in a polar and aprotic medium to acquire the designed molecules, 5a-g. These convergent derivatives were evaluated for their inhibitory potential against α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Acarbose was used as a reference standard for α-glucosidase inhibition while eserine for AChE and BChE inhibition. Some of the synthesized compounds were identified as promising inhibitors of these three enzymes and their bioactivity potentials were also supported by molecular docking study. The most active compounds among the synthetic analogues might be helpful in drug discovery and development for the treatment of type 2 diabetes and Alzhiemer's diseases.

Keywords: 2-Furoic piperazide; Cholinesterases; Enzyme inhibition; Molecular docking; Sulfonamide; α-Glucosidase.