Determination of affinity and efficacy of acetylcholinesterase inhibitors using isothermal titration calorimetry

Drączkowski, Piotr; Tomaszuk, Anna; Halczuk, Paweł; Strzemski, Maciej; Matosiuk, Dariusz; Jóźwiak, Krzysztof

doi:10.1016/j.bbagen.2015.11.006

Cited by 23 publications

(10 citation statements)

References 35 publications

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“…The 3-O-caffeoylquinic acid shows the most stable complex and strong interaction with AChE and also the highest inhibitory activity. KM of ACh hydrolysis by AChE according to Draczkowskiego amounts 73.9 μmol/L, and in our study it was evaluated at 48.5 μmol/L (Draczkowski et al 2016) and the differences might depend from the temperature of the experiment. The high value of Ki was showed by 4-O-caffeoylquinic acid 0.955 μmol/L, and its isomers 3-O-caffeoylquinic and 5-O-caffeoylqunic acids, the most abundant chlorogenic acids in coffee brews both exhibited Ki value at about 0.42 μmol/L.…”

Section: Inhibition Of Acetylcholinesterasementioning

confidence: 95%

Analysis of the Activity of Hydroxycinnamic Acids From Green and Roasted Coffee Extracts as Acetylcholinesterase Inhibitors Using an Isothermal Method of Titration Calorimetry

Grzelczyk¹,

Budryn²

2019

Folia Pomer. Univ. Technol. Stetin., Agric., Aliment., Pisc., Z

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Acetylcholinesterase (EC 3.1.1.7) is a major enzyme responsible for the pathogenesis of Alzheimer's disease (AD). This enzyme regulates the nerve impulse conduction by hydrolyzing the excess of acetylcholine in the synaptic cleft, decreasing its level in the brain. A low level of acetylcholine observed in neurodegenerative diseases contributes to the formation of amyloid plaques and neurofibrillary degeneration, which together with the development of AD spread in the cerebral cortex. That is why natural, non-toxic AChE inhibitors are sought for. The aim of the study was to assess the degree of inhibition of AChE activity by single hydroxycinnamic acids and coffee extracts depending on the type of coffee and its roasting. The study was carried out by means of isothermal titration calorimetry (ITC), determining thermodynamic interactions and parameters. ITC analysis showed that the most stable bonds and strong interactions were characterized by 3-caffeoylquinic acid with AChE, and also was the most effective AChE inhibitor. Analysis of coffee extracts showed that the highest activity to AChE was characterized by Robusta green coffee.

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Section: Inhibition Of Acetylcholinesterasementioning

confidence: 95%

Analysis of the Activity of Hydroxycinnamic Acids From Green and Roasted Coffee Extracts as Acetylcholinesterase Inhibitors Using an Isothermal Method of Titration Calorimetry

Grzelczyk¹,

Budryn²

2019

Folia Pomer. Univ. Technol. Stetin., Agric., Aliment., Pisc., Z

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“…One effective strategy for ameliorating the symptoms of AD is to enhance the acetylcholine (ACh) level via inhibiting the acetylcholine esterase enzyme in diseased brain [3]. But the serious side effects caused by licensed drugs used to treat AD have forced researchers to investigate safer acetylcholine esterase enzyme (AChE) inhibitors from natural sources [4,5]. Numerous plants and their constituents are reported in traditional medicine practices as AChE activity inhibitor to enhance cognitive function and alleviate other symptoms of AD [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Bioguided Isolation and Structure Identification of Acetylcholinesterase Enzyme Inhibitors from Drynariae Rhizome

Zeng

Shen

et al. 2020

Journal of Analytical Methods in Chemistry

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Drynariae Rhizome, widely distributed in southern China, was clinically used as a traditional treatment for cognitive disfunction, such as Alzheimer’s disease (AD). The aim of our work was to evaluate the AChE inhibition activities of extracts of Drynariae Rhizome and pure compounds using a bioguided fractionation procedure. The classical approach for screening potential AChE inhibitors was developed by Ellman. However, the background color of compounds or herb extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Here, a high-throughput assay monitoring the transformation of iodized choline from iodized acetylcholine catalyzed by AChE was established based on UPLC-MS/MS. The bioguided fractionation of the extract using this method resulted in the isolation of eight AChE inhibitory flavonoids, including naringenin, eriodictyol, kaempferol, luteolin, astragalin, luteolin-7-O-β-D-glucoside, naringin, and neoeriocitrin, with the IC50 values of 3.81 ± 0.21 μM, 7.19 ± 0.62 μM, 11.09 ± 1.02 μM, 17.26 ± 0.23 μM, 18.24 ± 2.33 μM, 17.13 ± 1.02 μM, 26.4 ± 1.17 μM, and 22.49 ± 1.25 μM. It is assumed that the identified flavonoids contribute to the AChE inhibition activity of Drynariae Rhizome. These results are in agreement with the traditional uses of Drynariae Rhizome for AD.

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“…Though numerous papers have already been published on enzyme kinetic measurements using microcalorimetry, only a few very recent articles have dealt with inhibition studies 9,10 . In some cases, product or substrate inhibitions have been studied 5,11,12 , but ITC has scarcely been applied to determine half maximal inhibitory concentration (IC 50 ).…”

Section: Introductionmentioning

confidence: 99%

Simple ITC method for activity and inhibition studies on human salivary α-amylase

Lehoczki

Szabó

Takács

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Isothermal titration calorimetry (ITC) has an increasing significance in enzyme kinetic studies owing to its general applicability and sensitivity. In the present work, we aimed at developing a simple ITC-based screening procedure for the measurement of human salivary a-amylase (HSA) activity. Reaction of two substrates was studied with three independent methods (ITC, HPLC and spectrophotometry). ITC experiments were made using free and chromophore-containing maltooligomers of different length as substrates. Detailed studies revealed that maltoheptaose or longer oligomers could model properly starch and the presence of aromatic chromophore group did not affect the K M values considerably. It is the first time, when ITC was used to investigate of HSA-catalysed hydrolysis of different substrates (2-chloro-4-nitrophenyl-4-O-a-Dgalactopyranosyl-maltoside, maltoheptaose and starch) in the presence of acarbose inhibitor. All measured IC 50 values are in micromolar range (0.9, 18.6 and 29.0 mM, respectively) and increased in parallel with the degree of polymerisation of substrates.

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Determination of affinity and efficacy of acetylcholinesterase inhibitors using isothermal titration calorimetry

Cited by 23 publications

References 35 publications

Analysis of the Activity of Hydroxycinnamic Acids From Green and Roasted Coffee Extracts as Acetylcholinesterase Inhibitors Using an Isothermal Method of Titration Calorimetry

Analysis of the Activity of Hydroxycinnamic Acids From Green and Roasted Coffee Extracts as Acetylcholinesterase Inhibitors Using an Isothermal Method of Titration Calorimetry

Bioguided Isolation and Structure Identification of Acetylcholinesterase Enzyme Inhibitors from Drynariae Rhizome

Simple ITC method for activity and inhibition studies on human salivary α-amylase

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