Novel diazen-bis(phenoxy-1,2,3-triazole-N-phenylacetamide) derivatives as potent anti-cholinesterase, anti-α-glycosidase and anti-a-amylase agents: <i>In vitro</i> and <i>in silico</i> evaluations

In this work, new diazen-bis(phenoxy-1,2,3-triazole-N-phenylacetamide) derivatives 9a-n were designed, synthesized, and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that are two important targets in the treatment of Alzheimer's disease (AD). These compounds were also evaluated against alpha-amylase and alpha-glycosidase because they were structurally similar to some inhibitors of these enzymes. In vitro evaluations demonstrated that, with the exception of alpha-glycosidase, most of the new synthesized compounds showed significant inhibitory effect against the studied enzymes. In this regard, the most potent compound against AChE and BChE (compound 9 h) was around 2 times more potent than standard inhibitor (tacrine) against these enzymes. Moreover, the most potent compound against alpha-amylase (compound 9i) was around 3.8 folds more potent than standard inhibitor (acarbose). Molecular modeling study demonstrated that these most potent compounds were attached to the active sites of the related target enzymes with the binding energies more favorable than used standard inhibitors. Furthermore, docking studies exhibited that compound 9 h interacted with both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of the binding sites AChE and BChE. These interactions are valuable to select a compound as the lead compound in the treatment of AD.

Dergi

JOURNAL OF MOLECULAR STRUCTURE

Yıl

2025

Cilt

1348

ISSN

0022-2860

eISSN

1872-8014

DOI

10.1016/j.molstruc.2025.143490

WoS UID

WOS:001631850700001