Substituted phenol and application thereof as receptor TR3 excitant

A technology of orphan receptors and phenol derivatives, applied in the field of substituted phenols

Inactive Publication Date: 2008-10-08
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this agonist cannot induce nuclear translocation of TR3

Method used

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  • Substituted phenol and application thereof as receptor TR3 excitant
  • Substituted phenol and application thereof as receptor TR3 excitant
  • Substituted phenol and application thereof as receptor TR3 excitant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1, detection of TR3 transcriptional activity

[0033] The reporter gene assay was used to detect the effect of the test compound on inducing the expression of the luciferase reporter gene, so as to reflect the level of TR3 transcriptional activity.

[0034] The test method is as follows:

[0035] Take 5×10 4 Inoculation amount of cells / well Cells were inoculated in a 24-well plate, and the receptor (TR3) expression vector, luciferase reporter gene plasmid (containing Luc-NurRE ) and β-galactosidase expression plasmids were transfected into HEK293T cells. After 24 hours of transfection, fresh complete culture medium was changed, and the treatment group was treated with the compound to be tested at the same time. Discard the culture medium after several hours of treatment, wash the cells twice with PBS, add 120 μl of lysate to each well, place at 4°C for 10 minutes, collect, centrifuge at 13,000 r / min for 5 minutes, and take the supernatant to measure luciferas...

Embodiment 2

[0039] Embodiment 2, in vitro antitumor activity detection

[0040] MTT (Methyl Thiazolyltetrazolium) method was used to detect the inhibitory effect of compounds on tumor cells in vitro.

[0041] The test method is as follows:

[0042] The cultured tumor cells (human B lymphoma Raji cells, human oral dermoid carcinoma KB cells and human gastric cancer cells BGC-823) were made into single cell suspension, counted by hemocytometer and diluted to a cell concentration of 6×10 4 individual / mL. Inoculate cells into 96-well plates, 80 μL per well. In addition, set 2 cells containing only 80 μL RMPI 1640 complete medium [cell culture medium: a bag of 10g dry powder RMPI 1640 (Gibco Co.Ltd.) cell culture medium was dissolved in 1L double distilled water; add 2g NaHCO 3 Stir well and dissolve, seal, and place at 4°C overnight to remove impurities by natural precipitation; add 10-15% inactivated (56°C, 30min) calf serum and 1% polyclonal antibody mother solution the next day; mix wel...

Embodiment 3

[0049] Embodiment 3, cell apoptosis analysis

[0050] DAPI staining and flow cytometry were used to detect the effect of compounds on inducing tumor cell apoptosis.

[0051] The test method is as follows:

[0052] DAPI-stained cell count: After treating the tumor cells with the compound to be tested (see the above-mentioned Example 1 for the method) for 24 hours, the tumor cells were washed twice with PBS, added with trypsin-EDTA digestion solution, and digested at 37° C. for 5 minutes. Pipette the cells, move to a centrifuge tube, and centrifuge at 800-1000r / min for 5min. Remove the digestion solution, add pre-cooled PBS, pipette to disperse the cells into a single-cell suspension as much as possible, centrifuge, repeat washing with cold PBS and resuspending the cells. Fix with 3.7% paraformaldehyde at 4° C. for 30 min, wash with PBS, and stain the cells with 50 μg / ml DAPI (containing 100 μg / ml RNase A) in the dark for 30 min. Wash twice with PBS, smear, observe the cells ...

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PUM

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Abstract

Disclosed are substituted benzene and the application thereof to be used as agonist for receptor TR3, relating to substituted benzene. The invention provides a substituted phenol derivative compound and the application thereof to be used as agonist for orphan receptor TR3, in particular to the application in preparing the medicine for curing hypoglycemia and diseases related to abnormal apoptosis of cells, such as cancer. The substituted benzene and the substituted phenol derivative compound are respectively denoted by structural formula I and structural formula II; wherein R1 is nitrophthalimides or other alcoxyl-acyl or alcoxyl-acyl-alkyl, R2 is n-octanoyl, or other alkyl-acyl, or alkyl-acyl-alkyl, or alkyl, and R3, R4, R5 and R6 are H, OH, NH2 or halogen atoms.

Description

technical field [0001] The present invention relates to a substituted phenol, in particular to a substituted phenol derivative compound and its use as a nuclear orphan receptor TR3 agonist in the preparation of medicines for treating cancer and other diseases associated with abnormal cell apoptosis and hypoglycemia use. Background technique [0002] The nuclear receptor superfamily (nuclear receptor superfamily) is a class of ligand-dependent transcription factors with many members, including steroid hormone receptors, thyroid hormone receptors, vitamin D3 receptors, retinoic acid receptors, retinol X receptors and Peroxisome proliferator-activated receptors, and a large number of orphan receptors (orphan receptors) discovered in recent years. Nuclear receptors are involved in the regulation of almost all physiological processes such as cell metabolism, growth, development, differentiation, death and immunity, and their abnormalities are closely related to many diseases of ...

Claims

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Application Information

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IPC IPC(8): C07C69/716C07D311/76A61K31/216A61K31/366A61P35/00A61P37/00A61P3/08
Inventor 沈月毛吴乔苏文金郑忠辉徐庆妍杜希萍黄耀坚宋思扬刘晶晶胡志钰
Owner XIAMEN UNIV
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