&lt;strong&gt;Synthesis, Characterization, Molecular docking and Structure-Activity Relationships of Novel 2-Arylidene- and 2-Aminomethylenethiazolo[3,2-&lt;em&gt;a&lt;/em&gt;]pyrimidines as Prospective Acetylcholinesterase Inhibitors&lt;/strong&gt;

Mohamed Y Mahgoub,Awatef M Elmaghraby,Gonçalo C Justino,M Matilde Marques,João L Ferreira Da Silva,Abd-Elfttah A Harb

doi:10.3390/ecmc-3-04682

Abstract

Acetylcholinesterase (AChE) is the enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine (ACh) into acetic acid and choline, a crucial mechanism for regulation of neurotransmission at synapses in all nervous systems. According to the cholinergic hypothesis, depleted levels of ACh are associated with Alzheimer's disease. As part of a program aimed at preparing new bioactive heterocycles with kinase and AChE inhibition properties, we designed and synthesized a series of (Z)-2-arylidene- and 2-aminomethylene derivatives of thiazolo[3,2-a]pyrimidine by a convenient multicomponent method. The products were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which indicated a consistent Z configuration at the arylidene and amino methylene double bond. Additionally, molecular docking simulations of the series of 2-arylidene/aminomethylene-thiazolo[3,2-a]pyrimidine derivatives to human AChE (PDB ID: 4m0f, chain A) were conducted to investigate the binding mode of those compounds in comparison to Territrem B, used as positive control. The results indicate that some of the test compounds have binding energies to AChE that are comparable, or better, than the positive control, Territrem B. Biological activity studies are underway to assess the activities of the new compounds [1-4].

Highlights

❖ Alzheimer’s disease (AD) was first identified more than 100 years ago. ❖ 70 years passed before AD was recognized as the most common cause of dementia, as well as a major cause of death in elderly people. ❖ Worldwide, nearly 47 million people have Alzheimer’s or a related dementia. ❖ The global cost of Alzheimer’s and dementia is estimated to be $605 billion
➢ Acetylcholinesterase (AChE) is the enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine (ACh) into acetic acid and choline
➢ According to the cholinergic hypothesis, depleted levels of ACh are associated with Alzheimer's disease

Summary

Introduction

❖ Alzheimer’s disease (AD) was first identified more than 100 years ago. ❖ 70 years passed before AD was recognized as the most common cause of dementia, as well as a major cause of death in elderly people. ❖ Worldwide, nearly 47 million people have Alzheimer’s or a related dementia (see map). ❖ The global cost of Alzheimer’s and dementia is estimated to be $605 billion. ❖ Alzheimer’s disease (AD) was first identified more than 100 years ago. ❖ 70 years passed before AD was recognized as the most common cause of dementia, as well as a major cause of death in elderly people.

Results

Conclusion