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Catechin derivative and use thereof in preparation of acetylcholinesterase activity inhibition medicines

A technology of catechin and derivatives, applied in the field of acetylcholinesterase inhibitors, to achieve the effect of inhibiting acetylcholinesterase activity, simple preparation method, and broad application prospects

Active Publication Date: 2016-12-21
ANHUI AGRICULTURAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] But at present, there is no report on the application of acylated catechin and its derivatives in inhibiting the activity of acetylcholinesterase

Method used

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  • Catechin derivative and use thereof in preparation of acetylcholinesterase activity inhibition medicines
  • Catechin derivative and use thereof in preparation of acetylcholinesterase activity inhibition medicines
  • Catechin derivative and use thereof in preparation of acetylcholinesterase activity inhibition medicines

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Preparation of catechin derivatives

[0037] 1.1 Description of catechin derivatives

[0038] The structure of catechin derivatives is shown in formula (I):

[0039]

[0040] When R 1 = H, R 2 When =OH, epicatechin trans-caffeate is formed;

[0041] When R 1 =OH,R 2 When =H, formed epigallocatechin trans p-coumarate;

[0042] When R 1 =OH,R 2 =OCH 3 When, epigallocatechin (3″-methoxy)-trans p-coumarate is formed.

[0043] 1.2 Specific preparation methods and results

[0044] (1) Get 4.5 kilograms of Zijuan tea, and pulverize Zijuan tea;

[0045] (2) First, 4.5 kg of pulverized Zijuan tea was leached with 15 liters of petroleum ether at room temperature for 72 hours, and then ultrasonically leached at 70 Hz for 2 hours to obtain a petroleum ether extract; leaching three times according to the above steps, combined extraction liquid and concentrate the extract to a paste to obtain 18 grams of petroleum ether extract;

[0046] Then the Zijuan tea extracted ...

Embodiment 2

[0077] Inhibitory Effect of Molecular Mimetic Catechin Derivatives on Acetylcholinesterase

[0078] Experimental method and results

[0079] Molecular docking was used to simulate the molecular binding modes of the above three catechin derivatives to acetylcholinesterase (AchE). The software used for molecular docking is AutoDock 4.2, and the corresponding scores can be obtained after the simulation ( E is the binding energy, Ki is the inhibition constant), the higher the score, the stronger the predicted affinity between the two. The binding amino acid residues found by molecular docking are:

[0080] Epicatechin trans-caffeate: Asp74, Ser125, Tyr133, Glu202, Phe295, Tyr337, Tyr341;

[0081] Epigallocatechin trans-p-coumarate: Tyr72, Asp74, Asn87, Tyr124, Glu202, Phe295, His447;

[0082] Epigallocatechin (3″-methoxy)-trans-p-coumarate: Tyr72, Asp74, Asn87, Tyr124, Glu202, Ser203, Tyr341, His447.

[0083] The docking results are as follows figure 1 , 2 , 3 shown. The ...

Embodiment 3

[0086] Verification of Inhibitory Effect of Catechin Derivatives on Acetylcholinesterase

[0087] 3.1 Experimental materials and reagents

[0088] Huperzine A, PBS buffer (pH 8.0±0.1), acetylcholinesterase (AchE) (0.25U·mL -1 ), thioacetylcholine iodide (ATCI) (0.0025mol L -1 ), 5,5-dithiodinitrobenzoic acid (DTNB) (0.003mol L -1 ), Dimethylsulfoxide (DMSO)

[0089] 3.2 Experimental methods and results

[0090] Add 160 μL of DTNB solution and 50 μL of AchE solution in 96-well plate, add 50, 10, 5, 1, 0.1 μmol·L respectively -1 Add 10 μL of epicatechin trans-caffeate solution, heat at 37°C for 20 minutes, add 30 μL of ATCI (solution, place in a microplate reader (25°C), record the A value of the reaction solution under visible light with a wavelength of 412nm .All samples were repeated 3 times and recorded as sample A. Replace AchE with 50 μL of PBS, replace the sample solution with 10 μL of DMSO, record it as A blank (repeat 3 times), and do blank zero adjustment. Replace...

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Abstract

The invention discloses a catechin derivative with the structure represented by formula (I) shown in the description. In the formula (I), R1 and R2 are respectively independently selected from H, OH and OCH3. The catechin derivative with the structure represented by formula (I) is extracted from Zijuan tea for the first time. The catechin derivative has a strong acetylcholinesterase inhibition effect, and the IC50 value of the catechin derivative can reach 2.33 [mu]M, 11.33 [mu]M and 62.10 [mu]M, so the catechin derivative has an acetylcholinesterase activity inhibition effect, has wide application prospect in finding and preparation of anti-acetylcholinesterase medicines, and provides a research direction for researches of the preparation of the anti-acetylcholinesterase medicines.

Description

technical field [0001] The invention relates to an acetylcholinesterase inhibitor, in particular to a catechin derivative and its use in the preparation of a drug for inhibiting the activity of acetylcholinesterase. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is a chronic neurodegenerative disease mainly characterized by progressive cognitive impairment and memory impairment. Clinically, the main manifestations are cognitive decline, mental symptoms and behavioral disorders, and a gradual decline in the ability of daily life. [0003] At present, obtaining acetylcholinesterase inhibitors through screening is one of the most important ways to find effective drugs for the treatment of Alzheimer's disease (AD). Known acetylcholinesterase inhibitors mainly include: tacrine, donepezil, galantamine, risdigmine, metriphosphatidylcholine, estigmine, and huperzine A. These inhibitors can inhibit the activity of acetylcholinesterase (AchE),...

Claims

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Application Information

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IPC IPC(8): C07D311/74A61P25/28
CPCC07D311/74
Inventor 鲍官虎王威华芳
Owner ANHUI AGRICULTURAL UNIVERSITY
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