Novel coumarin derivatives bearing N-benzyl pyridinium moiety: Potent and dual binding site acetylcholinesterase inhibitors

Discovery of isoalloxazine derivatives as a new class of potential anti-Alzheimer agents and their synthesis

“…8 Therefore both these enzymes emerge as appropriate targets for the development of cholinesterase inhibitors in the treatment of AD. 9 Although AChE and BuChE are produced by different genes they are highly homologous with more than 65% similarity. AChE has two major binding sub-sites, a peripheral anionic site (PAS) and the other a catalyatic anionic site (CAS) which is located in the deep gorge of the enzyme structure and is assigned to Ser-His-Glu catalytic triad.…”

Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors

“…Recently, some compounds with potent AChE inhibition activities were reported, in which, N-benzyl pyridinium moiety was introduced into a series of aromatic scaffolds and emerged as an essential structure for inhibition of AChE ( Figure 1). [22][23][24][25][26] Meanwhile, docking studies have revealed that the presence of N-benzyl pyridinium moiety contributed to inhibitor activity by interacting with CAS, and the aromatic part of the hetero rings might engage to favorable stacking interactions with PAS of AChE. These findings led us to propose a series of novel 4-isochromanone compounds through hybridization approach ( Figure 1).…”

Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

“…[9][10][11][12] Many reports indicated that compounds bearing aromatic/ heteroaromatic rings on lateral parts of pyridinium displayed high AChE inhibitory activity and act as dual binding inhibitors. [13][14][15][16] According to the docking studies of these compounds, it was found that both terminal rings attached to the pyridinium were able to bind simultaneously to both CAS and PAS of the enzyme resulting in higher AChE inhibitory activity. [13][14][15][16] Among the reported studies, pyridinium derivatives having benzofuran ring were shown to have a significant AChE inhibitory activity and it was observed that benzofuran and phenyl moieties as terminal rings were interacted with both PAS and CAS of AChE.…”

“…[13][14][15][16] According to the docking studies of these compounds, it was found that both terminal rings attached to the pyridinium were able to bind simultaneously to both CAS and PAS of the enzyme resulting in higher AChE inhibitory activity. [13][14][15][16] Among the reported studies, pyridinium derivatives having benzofuran ring were shown to have a significant AChE inhibitory activity and it was observed that benzofuran and phenyl moieties as terminal rings were interacted with both PAS and CAS of AChE. 15,16) On the other hand, many of compounds bearing hydrazonehydrazide functional group have been reported to possess ChE inhibitory activity.…”