Comparison of active sites of butyrylcholinesterase and acetylcholinesterase based on inhibition by geometric isomers of benzene‐di‐<i>N</i>‐substituted carbamates

Chiou, Shyh‐Ying; Huang, Chin-Shiu; Hwang, Mei-Ting; Gao, Lin

doi:10.1002/jbt.20286

Cited by 26 publications

(19 citation statements)

References 21 publications

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“…The slope of the line revealed the number of Trp located in the active centre equals to 1(n & 0.98). Trp may serves as an anionic binding site in the process of catalytic reaction (Chiou et al 2009), and modification of this Trp will lead to complete inactivation. According to this characteristic, fluorescence spectroscopy will be an appropriate technique to exploit its possible structure changes for additional substances and variation of microenvironment in the active site.…”

Section: Effect Of Metal Ionsmentioning

confidence: 99%

Catalytic characteristics of plant-esterase from wheat flour

Hou

Yang

et al. 2011

World J Microbiol Biotechnol

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A plant-esterase extracted from wheat flour and purified with a PEG1000/NaH(2)PO(4) aqueous two-phase system was characterized for its catalytic characteristics. The optimal condition for plant-esterase to catalyze 1-naphthyl acetate was at 30°C, pH 6.5. It kept stability at 20°C during 120 min and at pH 5.5 during 60 h. The effects of metal ions, chemical modification reagents and pesticides on plant-esterase activity were investigated. It was found that Ba(2+) and Pb(2+) at concentrations of 20 mM significantly inhibited the activity of plant-esterase while Mg(2+), Ca(2+) and Fe(2+) at the same concentration enhanced the enzyme activity. Chemical modification reagents significantly influenced the activity of plant-esterase. Particularly, PMSF (4.5 mM) and N-bromosuccinimide (11 mM) inhibited by 5.40-19.87% of the enzyme activity. It is implied that serine and tryptophan are related to the enzyme activity. Plant-esterase were displayed concentration-dependent inhibition by dichlorvos, carbofuran and carbendazim (IC50 = 0.31-63.12 ppm). All these results indicated that catalytic efficiency of plant-esterase strongly depends on reaction conditions, activity effectors and amino acid residues at the active site. It makes meaningful guidance on further design of sensing material in monitoring pesticides.

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Section: Effect Of Metal Ionsmentioning

confidence: 99%

Catalytic characteristics of plant-esterase from wheat flour

Hou

Yang

et al. 2011

World J Microbiol Biotechnol

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“…The indole of this amino acid creates a π–π interaction with the 1-indanone ring. Furthermore, a hydrogen bond formation is observed between the carbonyl of the 1-indanone and the amine of Phe295 [ 22 , 23 , 24 , 60 , 61 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Structure–Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer’s Disease

et al. 2020

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Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 µM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 µM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.

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“…As a result, the binding site of BChE accommodated adamantyl derivatives (1-26) relatively well, compared to AChE. Adamentyl derivatives synthesized recently by our group could be considered as lead compounds for developing AD treatments, as some selective BChE inhibitors have already been reported to increase acetylcholine levels and to reduce the formation of abnormal amyloid found in Alzheimer's disease [22,23] .…”

Section: Introductionmentioning

confidence: 98%

In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes

et al. 2015

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Aim: To investigate the binding mode of synthesized adamantly derivatives inside of cholinesterase enzymes using molecular docking simulations. Methods: A series of hybrid compounds containing adamantane and hydrazide moieties was designed and synthesized. Their inhibitory activities against acetylcholinesterase (AChE) and (butyrylcholinesterase) BChE were assessed in vitro. The binding mode of the compounds inside cholinesterase enzymes was investigated using Surflex-Dock package of Sybyl7.3 software. Results: A total of 26 adamantyl derivatives were synthesized. Among them, adamantane-1-carboxylic acid hydrazide had an almost equal inhibitory activity towards both enzymes, whereas 10 other compounds exhibited moderate inhibitory activity against BChE. The molecular docking studies demonstrated that hydrophobic interactions between the compounds and their surrounding residues in the active site played predominant roles, while hydrophilic interactions were also found. When the compounds were docked inside each enzyme, they exhibited stronger interactions with BChE over AChE, possibly due to the larger active site of BChE. The binding affinities of the compounds for BChE and AChE estimated were in agreement with the experimental data. Conclusion:The new adamantly derivatives selectively inhibit BChE with respect to AChE, thus making them good candidates for testing the hypothesis that BChE inhibitors would be more efficient and better tolerated than AChE inhibitors in the treatment of Alzheimer's disease.

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Comparison of active sites of butyrylcholinesterase and acetylcholinesterase based on inhibition by geometric isomers of benzene‐di‐N‐substituted carbamates

Cited by 26 publications

References 21 publications

Catalytic characteristics of plant-esterase from wheat flour

Catalytic characteristics of plant-esterase from wheat flour

Design, Synthesis, and Structure–Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer’s Disease

In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes

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