Design and synthesis novel acetylcholinesterase inhibitors based on 2, 4-thiazolidindion and its molecular docking study

Hannaneh Naeimi kararoudi,1,* Hossein ghafoori,2 Asadollah mohammadi,3

1. Department of Biochemistry, Faculty of Sciences, University of Guilan
2. Department of Biochemistry, Faculty of Sciences, University of Guilan
3. Department of Chemistry, Faculty of Sciences, University of Guilan

Abstract

Introduction

Alzheimer disease (ad) is a neurodegenerative and progressive disorder of the brain and is the most common age-related dementia that results in the progressive and irreversible cognitive impairment, decline in language, memory loss, decreased ability to learn, and a severe compromise in thinking ability, judgment, and decision making. the ad is characterized by the two most neuropathological hallmarks, the presence of senile plaques and the neurofibrillary tangles, which are the result of the accumulation of beta-amyloid (aβ) peptide according to the beta-amyloid hypothesis, the accumulation and deposition of beta-amyloid in different areas of the brain causing a cascade of reactions that causes nervous disorders. it has also been shown in many studies that the acetylcholinesterase enzyme is likely to play a very important role in the formation of senile plaques by binding to beta-amyloid and accelerating its sedimentation. thus, several classes of ache inhibitors such as galanthamine, donepezil, rivastigmine and tacrine are the main stay drugs for the clinical management of ad and currently constitute the only fda-approved therapeutic approach. synthetic chemicals play a major role to meet increasing industrial and medicinal demands in the developing world. recently thiazolidine derivatives have attracted attentions with their versatile properties and they have been one of the important research focuses. 4-thiazolidinones are the derivatives of thiazolidine, which belong to an important group of heterocyclic compounds. diverse biological activities such as antibacterial, pesticidal, antifungal, insecticidal, anticonvulsant, tuberculostatic, anti-inflammatory, antithyroidal, antiviral, shp-2 inhibitor and calcium antagonist, potentiation of pentobarbital-induced sleeping time, etc., have been found to be associated with thiazolidinone derivatives. the purpose of the present study synthesis of a new derivative of 2, 4-thiazolidinone to inhibit ache involved in ad.

Methods

A new derivative of 2, 4-thiazolidinone in the reaction with 4-methoxybenzaldehyde was synthesized by the reflux column. verification of the structure of the new compound was investigated by ft-ir and nmr. the effect of the synthetic compound on the inhibition of ache was investigated. interactions between synthetic compound and ache were investigated by molecular docking.

Results

The synthesized derivative of 2, 4-thiazolidinone was confirmed by ft-ir and nmr. the effect of the synthesized compound on the inhibition of ache activity in 25 to 250 µm concentrations was investigated. the percentage of inhibition was calculated as control and 26 to 57% inhibition was observed in enzyme activity. a molecular docking study using the autodock 4.2 program represents an optimal interaction between the synthesis compound and ache.

Conclusion

Molecular docking studies on the new compound derived from 2, 4-thiazolidinone ache inhibitor represent an effective link between the ligand and the protein. the new compound also significantly inhibits the activity of the ache.

Keywords

Acetylcholinesterase, 2, 4-thiazolidinone, molecular docking