A kind of gsk-3 inhibitor and its preparation method and application
A technology for pharmaceutical preparations and compounds, applied in the field of medicine, can solve the problems of limited effect and lack of drugs that can effectively reverse the AD process.
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Embodiment 2G
[0089] Embodiment 2 GSK-3 inhibitory activity experiment
[0090] 1. Test method:
[0091] Incubate the FAM-labeled substrate with kinase, ATP and a certain concentration of compound (from Example 1) solution at 28°C for 1 h, quench with a quencher, and measure the conversion rate of the substrate using a Caliper instrument. The better the inhibition, the lower the conversion value. The results are shown in Table 1.
[0092] 2. Test results:
[0093] Table 1 Compounds of the present invention have inhibitory activity on GSK-3
[0094] compound GSK-3α% inhibition rate a
[0095] a Indicates the inhibition rate of different subtypes of GSK-3 at a concentration of 1 μM
Embodiment 3H2
[0096] Example 3H 2 o 2 Neuroprotective assay of induced oxidative damage to cells
[0097] 1. Test method:
[0098] Seed PC12 cells on a 96-well plate at 37°C, 5% CO 2 Incubate in an incubator for 24h, suck out the medium, add different concentrations of compounds (from Example 1) and 150 μM H 2 o2 , set at 37°C, 5% CO 2 Incubate in the incubator for 24h and measure the survival rate of the compound on PC12 cells by tetramethylazolium salt (MTT) colorimetric method.
[0099] 2. Experimental results:
[0100] See the experimental results figure 1 ,Depend on figure 1 It can be seen that when adding H 2 o 2 , the survival rate of PC12 nerve cells was significantly reduced, only 58.2%. When compound I-1, I-2 and I-5 are added, they can all show protection to PC12 nerve cells at different concentrations, and the higher the concentration, the better the protective performance. When the concentration is 10 μM, the cell survival rate All were above 70%, and the positive...
Embodiment 4
[0101] Example 4Cu 2+ Induced Aβ aggregation inhibition assay
[0102] 1. Test method:
[0103] Take HEPES as a blank control, take 20 μL of 40 μM Aβ 42 monomer solution and 20 μL of 40 μM CuCl 2 The solution was placed in a 96-well plate, 40 μL of HEPES or 40 μM compound (from Example 1) solution was added, and incubated at 37° C. under a shaker for 24 h. Add 120 μL Thioflavin T solution, place in a multifunctional microplate reader, shake for 2 minutes, and measure the fluorescence value at an excitation wavelength of 450 nm and an emission wavelength of 485 nm.
[0104] 2. Experimental results:
[0105] See the experimental results figure 2 ,Depend on figure 2 It can be seen that Cu 2+ It can induce the aggregation of Aβ and increase the degree of aggregation of Aβ. Taking the fluorescence intensity of Aβ self-polymerization as 100%, when adding Aβ and Cu 2+ Afterwards the fluorescence intensity value increased to 108.6%. After adding compound or positive cont...
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Abstract
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