Design and synthesis a new derivative of 2,4-thiazolidinone and studying molecular docking and its effect on inhibiting acetylcholineesterase
Hannaneh Naeimi kararoudi
,1,* Hossein ghafoori
,2 Asadollah mohammadi
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
Alzheimer’s disease (ad) is a progressive, degenerative disorder of the brain and is the most common form of dementia among the elderly especially in industrialized countries. according to the cholinergic hypothesis, the decreased levels of acetylcholine in the brain areas dealing with learning, memory, behavior, and emotional responses are of critical importance in ad. the reduced levels of neurotransmitter acetylcholine are due to its rapid hydrolysis by an enzyme, acetylcholinesterase (ache). there have also been several reports showing that the enzyme ache plays a key role in the development of the senile plaques by accelerating amyloid-beta deposition. thus, ache inhibition has been documented as a critical target for the
effective management of ad by an increase in the availability of acetylcholine in the brain regions and decrease in the deposition of amyloid beta. the current standard of care for
mild to moderate ad, based on the so-called cholinergic hypothesis, includes treatment with ache inhibitors (acheis) to improve cognitive function. several classes of acheis such as donepezil, rivastigmine, and galantamine were developed to purposely treat ad, and currently constitute the only fda-approved therapeutic approach. one of the main objectives of organic and medicinal chemistry is the design, synthesis and production of molecules having value as human therapeutic agents. during the past decade, combinatorial chemistry has provided access to chemical libraries based on privileged structures, with heterocyclic structures receiving special attention as they belong to a class of compounds with proven utility in medicinal chemistry. there are numerous biologically active molecules with five membered rings, containing two hetero atoms. thiazolidinone is an important scaffold known to be associated with several biological activities. the 4-thiazolidinone scaffold is very versatile and has featured in a number of clinically used drugs. they have found uses as antitubercular, antimicrobial, anti-inflammatory and as antiviral agents, especially as anti-hiv agents. the aim of this study is to provide new compounds derived from 2,4-thiazolidinone to inhibit ache involved in ad.
Synthesis of the new compound of the reaction of 2,4-thiazolidinone and 2-hydroxybenzaldehyde was performed using a reflux column. approved the structure of the synthesized compound by using the ft-ir and nmr were investigated. the effect of the new compound on the inhibition of ache was investigated. frap test was used to study the antioxidant activity of the synthesis compound. also, using molecular docking, interaction between the synthesis compound and ache were studied.
The structure of the new compound was approved by the ft-ir and nmr. the effect of the synthetic compound on the inhibition of ache activity in 25 to 250 µm concentrations was investigated and in a dose-dependent manner, 16 to 63% inhibitory activity was observed in enzyme activity. to evaluate the antioxidant activity, a concentration of 1 mm synthetic compound was used in different volumes and the results were all in the standard chart. investigation the interactions between synthetic compounds and ache by program autodock 4.2 indicates a good binding energy.
Studies conducted on the synthesized new compound indicate the proper interaction between the compound and the ache and also have a good potential for inhibiting ache activity. analyzing the antioxidant activity of the compound also shows its sensible reduction properties.
Acetylcholinesterase, 2,4-thiazolidinone, molecular docking, frap test