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Imidazo[1,2-A]pyridine Mannich Bases: Synthesis, Anticholinesterase Evaluation, and in Silico Studies

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Date

2025

Journal Title

Journal ISSN

Volume Title

Publisher

Springer int Publ Ag

Abstract

In this study, a series of imidazo[1,2-a]pyridine-mannich bases were designed and synthesized for the inhibition of cholinesterases, one of the important pathways in the treatment of Alzheimer's dementia. The imidazopyridine scaffold, which is found in the structure of many active compounds in pharmaceutical use, is derived from Mannich-bases containing morpholine and various aromatic groups. In vitro AChE and BChE enzyme activities and enzyme kinetics studies of new potential drug candidates (9a-j) that can target the critical binding regions of cholinesterases were conducted. In vitro evaluation with donepezil, tacrine (control compounds), and 9a-j, it was found that naphthalene-substituted compound 9j exhibited the most potential anti-cholinesterase activity (IC50s: 57.75 nM for AChE; 99.0 nM for BChE). Molecular docking studies performed with hAChE and hBChE enzyme crystal structures revealed that compound 9j has a higher binding affinity by targeting the CAS and PAS binding sites. Additionally, drug-likeness and pre-ADMET evaluation of the compounds showed that compound 9j had the most favorable drug properties. These results might be a new milestone in terms of the promising importance of the imidazopyridine scaffold in future drug design for the treatment of AD.

Description

Kuzu, Burak/0000-0002-7305-7177

Keywords

Imidazopyridine, Mannich, Anti-Cholinesterase, Molecular Docking, Pre-Admet

Turkish CoHE Thesis Center URL

WoS Q

N/A

Scopus Q

Q3

Source

Volume

79

Issue

3

Start Page

2005

End Page

2018