Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors

Abstract

The present study describes the synthesis of a novel series of thiazolidin-4-one and thiazinan-4-one using 1-(2-aminoethyl)pyrrolidine as amine precursor. All compounds were synthesised by one-pot three component cyclocondensation reaction from the amine, a substituted benzaldehyde and a mercaptocarboxylic acid. The compounds were obtained in moderate to good yields and were identified and characterised by 1 H, 13 C, 2 D NMR and GC/MS techniques. The compounds also were screened for their in vitro acetylcholinesterase (AChE) activity in hippocampus and cerebral cortex on Wistar rats. The six most potent compounds have been investigated for their cytotoxicity by cell viability assay of astrocyte primary culture, an important cell of central nervous system. We highlighted two compounds (6a and 6k) that had the lowest IC 50 in hippocampus (5.20 and 4.46 mM) and cerebral cortex (7.40 and 6.83 mM). These preliminary and important results could be considered a starting point for the development of new AChE inhibitory agents.

Synthesis, In Silico and Pharmacological Evaluation of New Thiazolidine-4-Carboxylic Acid Derivatives Against Ethanol-Induced Neurodegeneration and Memory Impairment

“…12,13 Furthermore, many thiazolidines are screened for their potential anti-inflammatory, antiviral, anticancer, antimicrobial, acetyl/butyrylcholinesterase inhibition, neuroprotective, antinociceptive, immunostimulant, and hepatoprotective properties. 12,[14][15][16][17][18][19] Likely, these compounds exhibited potent-free radical scavenging properties as demonstrated in several reports [20][21][22][23][24] which can be attributed to neuroprotection in Parkinson's 25,26 Alzheimer's, 27 and other memory impairment models. 28 In this context, the beneficial effects of thiazolidines against multiple Alzheimer's targets have been recently reviewed.…”

An Insight into 4-Thiazolidinones

“…Molecular docking study has also been performed to know the binding mode of these analogs in to their active sites of enzymes responsible for their corresponding diseases. Thus we can conclude that thiazolidinone is a novel potentially active nucleus and also a promising scaffold for synthesis of other compounds [42].…”

“…The inhibition of the AChE enzyme results in the blockage of ACh hydrolysis. All compounds were again synthesised by one-pot three component cyclocondensation reaction from the amine, a substituted benzaldehyde and a mercaptocarboxylic acid [42][43][44][45].…”

Synthesis of New 3-Arylcoumarins Bearing N-Benzyl Triazole Moiety: Dual Lipoxygenase and Butyrylcholinesterase Inhibitors With Anti-Amyloid Aggregation and Neuroprotective Properties Against Alzheimer’s Disease

“…During the last 40 years, tacrine, donepezil, rivastigmine, and galantamine were the only four cholinesterase inhibitors launched in the market ( De Simone et al, 2020 ; Miranda et al, 2020 ) for AD treatment. The high failure rate (99.6%) of the anti-AD drugs entered in clinical trials to meet the prefixed clinical endpoints from 2002 to 2012 clearly demonstrates the urgent and unmet need for the development of new anti-AD drugs with different mechanisms of action ( Das Neves et al, 2019 ).…”