Title : Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer's disease - Pourtaher_2022_Sci.Rep_12_15236 |
Author(s) : Pourtaher H , Hasaninejad A , Iraji A |
Ref : Sci Rep , 12 :15236 , 2022 |
Abstract :
The objective of this study was to design new polysubstituted pyrrole derivatives as selective acetylcholinesterase (AChE) inhibitors to target Alzheimer's disease. In this context, a highly efficient, one-pot, sequential, multi-component synthesis of a diverse range of polysubstituted pyrroles was developed through a sequential domino strategy by the condensation of amines with 1,1-bis(methylthio)-2-nitroethene (BMTNE), Knovenagle reaction of arylglyoxals with malono derivatives and subsequent Michael addition and intramolecular cyclization reaction in EtOH at reflux. Thirty-nine synthesized compounds were evaluated as AChE and butyrylcholinesterase (BChE) inhibitors. Among the synthesized compounds, compound 4ad (IC(50) = 2.95 +/- 1.31 microM) was the most potent and selective AChE inhibitor with no significant inhibition against butyrylcholinesterase BChE. A kinetic study of 4ad revealed that this compound inhibited AChE in an uncompetitive mode. Based on a molecular modeling study, compound 4ad due to its small size properly fitted into the active site of AChE compared to BChE and stabilized by H-bond and hydrophobic interactions with the critical residues of the AChE binding pocket. Consequently, it was proposed that the 4ad derivative can be an ideal lead candidate against AD with a simple and practical operation of synthetic procedures. |
PubMedSearch : Pourtaher_2022_Sci.Rep_12_15236 |
PubMedID: 36075926 |
Pourtaher H, Hasaninejad A, Iraji A (2022)
Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer's disease
Sci Rep
12 :15236
Pourtaher H, Hasaninejad A, Iraji A (2022)
Sci Rep
12 :15236