Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on MRP2/3

A compound and hepatotoxicity technology, which is applied in the field of rapid screening of hepatotoxic compounds in Polygonum multiflorum, can solve problems affecting chemotherapy drug resistance and other issues

Pending Publication Date: 2021-09-10
NAT INST FOR FOOD & DRUG CONTROL
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have found that the half-inhibitory concentration of doxorubicin and pirarubicin, which are chemotherapy drugs for hilar cholangiocarcinoma, is correlated with the expression of MRP3, so the expression of MRP3 may affect the resistance of some chemotherapy drugs

Method used

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  • Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on MRP2/3
  • Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on MRP2/3
  • Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on MRP2/3

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 Computer Molecular Docking Screening of Hepatotoxic Compounds

[0061] The main components of Radix Polygoni Multiflori were collected through literature and database retrieval, and a total of 49 molecules were obtained. DiscoveryStudio2.5 was used to preprocess these molecules. The preprocessing mainly included the following operations: three-dimensional structure generation, structure optimization, and repeated structure deletion. 49 molecules were obtained. Chemical structures, based on which ligand libraries are constructed and subsequently used for virtual screening.

[0062] The Swiss-model database was searched with the keywords "MRP2" and "MRP3", and a homology model structure was obtained according to the screening rules. The template PDB number of MRP2 and MRP3 was 6uy0. According to literature [1-2] The recorded amino acid residues define the active site, and MRP2 has a radius of 位点的三维坐标位置为157.158707,176.372707,163.243586,其关键氨基酸残基为LYS295、VAL434、S...

Embodiment 2

[0084] Example 2 Hepatotoxicity investigation

[0085] In order to further verify the accuracy of the method in Example 1 and the correlation between MRP2 / 3 inhibition and liver toxicity, this example conducted a hepatotoxicity investigation.

[0086] HepaRG cells in the logarithmic growth phase were digested and adjusted to 5×10 4 cells / mL, inoculate about 5000 cells per well in a 96-well plate, and administer after incubation for 18-24 hours. A blank control group (without HepaRG cells), a vehicle control group (0.5% DMSO), a positive control group (MRP2 / MRP3 inhibitors) and different concentrations of target compound administration groups were set up. Firstly, a preliminary experiment was carried out according to the solubility of the compound in the solvent, and the concentration range of each target compound was preliminarily determined, and then further toxicity tests were carried out according to the results of the preliminary experiment to determine the half-inhibitor...

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Abstract

The invention relates to a method for screening hepatotoxic compounds in polygonum multiflorum based on a computer molecular docking technology. The method comprises the following steps: (1) obtaining a three-dimensional chemical structure of at least one compound to be detected in the polygonum multiflorum; (2) obtaining protein homologous modeling structures of the MRP2 and the MRP3, and respectively determining active sites of the MRP2 and the MRP3; (3) respectively carrying out computer molecular docking on the compound to be detected, a positive compound 1 with an MRP2 inhibition effect and a positive compound 2 with an MRP3 inhibition effect with the active sites to obtain docking scores; and (4) judging the to-be-detected compound as the hepatotoxic compound under the condition that the docking score of the to-be-detected compound reaches a docking judgment value. The screening method disclosed by the invention is rapid, economical and simple to operate, and can realize high-throughput screening of numerous compounds.

Description

technical field [0001] The present invention relates to a rapid screening method for hepatotoxic compounds in Radix Polygoni Multiflori, in particular to a method based on molecular docking technology using multidrug resistance-associated protein 2 (multidrug resistance-associated protein 2, MRP2) or multidrug resistance-associated protein 3 ( Multidrug resistance-associated protein 3, MRP3) is a screening method for hepatotoxic compounds in Radix Polygonum multiflorum with the target. Background technique [0002] Polygonum multiflorum is the dry tuber root of Polygonum multiflorum Thunb., which has the functions of nourishing liver and kidney, nourishing essence and blood, and black hair. Recently, the toxicity of Polygonum multiflorum has become increasingly prominent. The Adverse Reaction Monitoring Center of the State Food and Drug Administration (SFDA) has collected more than 20,000 adverse reaction reports of Polygonum multiflorum preparations (involving more than 1,0...

Claims

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Application Information

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IPC IPC(8): G16C20/64G16C20/30G16C20/90G16C20/20G16C20/50G16C10/00G16B15/30G16B50/30
CPCG16C20/64G16C20/30G16C20/90G16C20/20G16C20/50G16C10/00G16B15/30G16B50/30
Inventor 马双成汪祺文海若李勇杨建波于建东姚令文
Owner NAT INST FOR FOOD & DRUG CONTROL
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