CN112138005A - NAT10 inhibitor analogue with colon cancer treatment function and application thereof - Google Patents

NAT10 inhibitor analogue with colon cancer treatment function and application thereof Download PDF

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CN112138005A
CN112138005A CN202010968594.0A CN202010968594A CN112138005A CN 112138005 A CN112138005 A CN 112138005A CN 202010968594 A CN202010968594 A CN 202010968594A CN 112138005 A CN112138005 A CN 112138005A
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amine
colon cancer
thiazole
vinyl phenyl
analog
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宋宇
律海峡
孙堂强
段迎超
房立真
白素平
尹志奎
张慧
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Xinxiang Medical University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The invention provides a NAT10 inhibitor analogue with a colon cancer treatment function and application thereof, and relates to the technical field of biological medicines. The analogue has the effects of inhibiting the proliferation of colon cancer cells and promoting the apoptosis of the colon cancer cells, and compared with a blank control group, the survival rate of the cells has a significant difference (P) from the dosage of 8 mu mol/L<0.05), in a dose-dependent relationship; semi-inhibitory concentration IC50The value was 51.2. mu. mol/L; can obviously increase the apoptosis rate, and the apoptosis rate gradually increases along with the gradual increase of the dosage, and is in a dosage dependent relationship. The analogue can obviously increase the activity of Caspase-3, 9 and is in a dose-dependent relationship. 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase Bax mRNA expression and reduce Bcl-2mRNA expression, and is in dose-dependent relationshipIs described.

Description

NAT10 inhibitor analogue with colon cancer treatment function and application thereof
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a NAT10 inhibitor analogue with a colon cancer treatment function and application thereof.
Background
China is a country with high incidence of colon cancer, and the research on the pathogenesis of colon cancer is remarkably improved in recent 20 years, but effective treatment measures are still lacked in the aspect of treatment[1-2]. In terms of pathogenesis, since the P53 mutation is discovered for the first time, with the identification of the mutation field and the detailed molecular category in recent years, great progress has been made[3]. NAT10 was found to act as an enhancer of telomerase activity by stimulating transcription of hTERT[4]. The protein consists of 872 amino acids, has an acetyltransferase domain and a lysine-rich C-terminal[5-6]. In other studies, it was found that the involvement of NAT10 in histone and microtubule modification plays a crucial role in the generation mechanism of tumors[7]The inhibition of NAT10 by the NAT10 inhibitor Remodelin can reduce the resistance of breast cancer cells to adriamycin[8]. Through the research, the NAT10 inhibitor can generate a correlation in the formation mechanism of liver cancer tumors by inhibiting the expression of NAT10, NAT10 (N-acetyltransferase) is widely existed in cells, is a nucleoprotein consisting of 872 amino acids, comprises an acetyltransferase structural domain and a carboxyl terminal rich in lysine (mainly used for regulating the activity of telomerase)[9-10]The research shows that NAT10 is related to the development of various tumors. And is associated with a shorter patient life[11-12]。
Reference documents:
[1]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].Ca Cancer J Clin,2015,65(2):87-108.
[2]Strillacci A,Griffoni C,Lazzarini G,et al.Selective cyclooxygenase-2 silencing mediated by engineered E.coli and RNA interference in-duces anti-tumour effects in human colon cancer cells[J].Br J Can-cer,2010,103(7):975-986.
[3]Hyndman KA,Knepper MA.Dynamic regulation of lysine acetylation:the balance between acetyltransferase and deacetylase activities[J].American journal of physiology Renal physiology,2017,313(4):F842-f846.
[4]Lv JJ,Liu HJ,Wang Q,et al..Molecular cloning of a novel human gene en-coding histone acetyltransferase-like protein involved in transcriptional activation of hTERT.Bioche Biophy Res Commun 2003；311:506-513.
[5]Shen,Q.,Zheng,X.,McNutt,et al.()NAT10,a nucleolar protein,localizes to the midbody and regulates cytokinesis and acetylation of microtubules.Exp.Cell Res.2009,315,1653-1667.
[6]Liu,X.,Tan,Y.,Zhang,C.,et al.()NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2.EMBO Rep.2016,17,349-366.
[7]X.Zhang,J.Liu,S.Yan,et al.High expression of N-ace-tyltransferase10:a novel independent prognostic marker of worse outcome in patients with hepatocellular carcinoma,Int.J.Clin.Exp.Pathol.2015,8:14765-14771.
[8]J.Wu,H.Zhu,J.Wu,et al.Inhibition of N-acetyltransferase 10 using remodelin attenuates doxorubicin resistance by reversing theepithelial-mesenchymal transition in breast cancer,Am J Transl Res 2018,10:256-0264.
[9]Yuqin Tana,Jiaojiao Zheng a,Xiaofeng Liu b,et al.Loss of nucleolar localization of NAT10 promotes cell migration andinvasion in hepatocellular carcinoma.Biochemical and Biophysical Research Communications[J].2018,499:1032-1038.
[10]Xiuming Zhang,Jimin Liu,Sheng Yan,et al.High expression of N-acetyltransferase 10:a novel independent prognostic marker of worse outcome in patients with hepatocellular carcinoma.Int J Clin Exp Pathol[J].2015,8(11):14765-14771.
[11]Qijiong Li,Xiaofeng Liu,Kemin Jin,et al.NAT10 is upregulated in hepatocellular carcinoma and enhances mutant p53 activity[J].BMC Cancer,2017,17:605.
[12] the influence and mechanism of ginkgolide on apoptosis and angiogenesis of vascular endothelial cells of hypoxia treated human being [ J ] is reported by second university of military medicine, 2020, 6 (24): 1-7.
Disclosure of Invention
In view of the above, the invention aims to provide a NAT10 inhibitor analog 4- (4-vinylphenyl) -1, 3-thiazole-2-amine with a function of treating colon cancer and an application thereof, wherein the analog can inhibit colon cancer cell proliferation, promote colon cancer cell apoptosis and has a potential value of treating colon cancer.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine with a function of treating colon cancer, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000031
preferably, the analog 4- (4-vinylphenyl) -1,3-thiazol-2-amine has a Compound CID of 684149 and a formula C11H10N2S, molecular weight 202.28 g/mol.
The invention also provides application of the analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in preparing a medicine for treating colon cancer.
The invention also provides application of the analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in preparing a medicament for inhibiting colon cancer cell proliferation.
The invention also provides application of the analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in preparing a medicament for promoting colon cancer cell apoptosis.
The invention also provides a medicine for treating colon cancer, the active ingredient of the medicine comprises NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000032
preferably, the medicament can promote the apoptosis of colon cancer cells and inhibit the proliferation of the colon cancer cells.
The invention also provides an inhibitor for colon cancer cell proliferation, the effective component of the medicine comprises NAT10 inhibitor analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000041
the invention also provides a promoter for colon cancer cell apoptosis, the effective component of the drug comprises NAT10 inhibitor analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000042
preferably, the promoter can reduce the expression of anti-apoptotic protein Bcl-2mRNA, and increase the content of the pro-apoptotic protein Caspase-3, 9 and the expression of Bax mRNA.
The invention provides a NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine with a colon cancer treatment function, which has the effects of inhibiting colon cancer cell proliferation and promoting colon cancer cell apoptosis. In the examples of the present invention, the results of the CCK8 test for in vitro evaluation of antitumor activity showed that the cell survival rate was from 8 μmo as the dose compared to the group without drugThe onset of a significant difference in L/L (P)<0.05). With increasing dose, cell survival rate decreased gradually, in a dose-dependent relationship. Half inhibitory concentration IC at 48h50The value was 51.2. mu. mol/L. The apoptosis condition is further detected by a flow cytometer, and the result shows that the apoptosis rate is remarkably different from the dosage of 8 mu mol/L (P) compared with the group without the drug<0.05). 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase the apoptosis rate. The apoptosis rate of the cells is gradually increased along with the gradual increase of the dosage, and the apoptosis rate is in a dosage-dependent relationship. The ELISA detects the activity of the Caspase-3, 9 in the cells, and the result shows that the activity of the Caspase-3, 9 in the cells is remarkably different from that in a drug-free group from 8 mu mol/L (P)<0.05). 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase the activity of Caspase-3, 9. With the gradual increase of the dosage of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the activity of Caspase-3, 9 is gradually increased in a dosage-dependent relationship. The expression of Bcl-2 and Bax mRNA in the cells is detected by qPCR, and the result shows that the expression of the Bcl-2mRNA and the Bax mRNA in the cells is remarkably different from that in a drug-free group from 8 mu mol/L (P)<0.05). 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase BaxmRNA expression and reduce Bcl-2mRNA expression. With the gradual increase of the dose of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the expression of Bax mRNA is gradually increased, and the expression of Bcl-2mRNA is gradually reduced in a dose-dependent relationship.
Drawings
FIG. 1 is a graph of the growth inhibition effect of 4- (4-vinylphenyl) -1,3-thiazol-2-amine on human colon cancer cell lines, a bar graph represents the average value of three experiments, and an error line represents Standard Deviation (SD); p <0.05, same below, for each group compared to the non-dosed group;
FIG. 2 is a graph showing the effect of 4- (4-vinylphenyl) -1,3-thiazol-2-amine on intracellular Caspase-3 activity;
FIG. 3 is a graph showing the effect of 4- (4-vinylphenyl) -1,3-thiazol-2-amine on intracellular Caspase-9 activity;
FIG. 4 is the expression of intracellular Bcl-2mRNA by 4- (4-vinylphenyl) -1, 3-thiazol-2-amine;
FIG. 5 shows the expression of Bax mRNA in cells by 4- (4-vinylphenyl) -1, 3-thiazol-2-amine;
FIG. 6 shows the effect of 4- (4-vinylphenyl) -1,3-thiazol-2-amine on hct-116 tumor-bearing mice tumors.
Detailed Description
The invention provides a NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine with a function of treating colon cancer, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000051
the analogue 4- (4-vinylphenyl) -1,3-thiazol-2-amine according to the invention is preferably an analogue of the NAT10 inhibitor Remodellin with Compound CID 684149 and formula C11H10N2S, molecular weight 202.28 g/mol. The analogue has the function of treating colon cancer, preferably shows that the analogue can promote the apoptosis of colon cancer cells and inhibit the proliferation of the colon cancer cells, more preferably can reduce the expression of anti-apoptotic protein Bcl-2mRNA, and increase the content of apoptosis-promoting protein Caspase-3, 9 and the expression of Bax mRNA. In the examples of the present invention, the colon cancer HCT116 cells were used as an example to test the effect on colon cancer, but the effect cannot be considered as the full protection scope of the present invention. The source of the colon cancer HCT116 cells is not particularly limited in the present invention, and is preferably purchased from ATCC in the United states.
The invention also provides application of the analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in preparing a medicine for treating colon cancer. In the invention, the concentration of the analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in the medicament for acting is not less than 8 mu mol/L.
The invention also provides application of the analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in preparing a medicament for inhibiting colon cancer cell proliferation.
The invention also provides application of the analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine in preparing a medicament for promoting colon cancer cell apoptosis.
The invention also provides a medicine for treating colon cancer, the active ingredient of the medicine comprises NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000061
the medicine can promote the apoptosis of colon cancer cells and inhibit the proliferation of the colon cancer cells, and particularly, the content of apoptosis-promoting protein Caspase-3, 9 and the expression of Bax mRNA are increased.
The invention also provides an inhibitor for colon cancer cell proliferation, the effective component of the medicine comprises NAT10 inhibitor analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000062
the invention also provides a promoter for colon cancer cell apoptosis, the effective component of the drug comprises NAT10 inhibitor analogue 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure BDA0002683243720000063
the promoter can reduce the expression of anti-apoptosis protein Bcl-2mRNA, and increase the content of apoptosis-promoting protein Caspase-3, 9 and Bax mRNA expression.
The invention provides a NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine with colon cancer treatment function and application thereof, which are described in detail in the following examples, but the invention is not to be construed as limiting the scope of the invention.
Example 1
CCK8 experiment is adopted to evaluate the growth inhibition effect of 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine on HCT116 colon cancer cell line, the cell survival rate and IC50And (4) carrying out measurement. Colon cancer HCT116 cells at 2X 104Individual cells/well were seeded into 96-well plates and allowed to adhere overnight. The next day 0, 2, 4, 8, 16, 32, 64. mu. mol/L4- (4-vinylphenyl) -1,3-thiazol-2-amine was added, and after 48h 10. mu.L of CCK8 solution (MCE Corp. USA) was added to each well and incubated at 37 ℃ for 4 h. Absorbance was measured at 450nm using a microplate reader (Thermo full automatic MK3, Saimer Feishel USA). Calculation of cell viability and half inhibitory concentration IC50The value is obtained. Cell survival (%) × (drug-treated OD-blank OD)/(solvent-control OD-blank OD) × 100%.
As shown in FIG. 1, the cell viability was significantly different from that in the case of the drug-free group at the dose of 8. mu. mol/L (P)<0.05). With increasing dose, cell survival rate decreased gradually, in a dose-dependent relationship. Half inhibitory concentration IC at 48h50The value was 51.2. mu. mol/L.
Example 2
The apoptosis condition of the cells after the action of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is detected by using a flow cytometer. HCT116 cells were seeded in 6-well plates containing 2mL of medium per well, and after 24 hours 0, 2, 4, 8, 16, 32, 64. mu. mol/L4- (4-vinylphenyl) -1,3-thiazol-2-amine was added, after 48h incubation, cell suspensions were prepared after digesting each set of cells with 0.1% pancreatin (without EDTA). The cells were collected after centrifugation at 1000 r/min for 5min, 5. mu.l of Annexin-V and 10. mu.l of PI dye were added, respectively, and mixed well and reacted in dark for 15min, and the cells were apoptotic by flow cytometry (Millipore Guava easy cell, Merck Mitigo, USA) within 1 h.
As shown in Table 1, the apoptosis rate was significantly different from the dose of 8. mu. mol/L (P <0.05) compared to the drug-free group. 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase the apoptosis rate. With the gradual increase of the dose of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the apoptosis rate gradually increases and is in a dose-dependent relationship.
Effect of 4- (4-Vinylphenyl) -1,3-thiazol-2-amine on the apoptosis Rate of HCT-116 cells
Figure BDA0002683243720000072
Figure BDA0002683243720000071
Note: p <0.05 compared to 0 umol/L; p <0.01 compared to 0 umol/L;
example 3
And (3) detecting the activity of Caspase-3, 9 in the cells. Caspase-3, 9 activity in cells is detected by applying a Caspase-3, 9 activity detection kit (Aimeijie Biotech, Inc.). After each group of cells are acted for 48 hours by 0, 2, 4, 8, 16, 32 and 64 umol/L4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the supernatant culture solution is discarded, the cells are digested by pancreatin, and the cells are collected to the spare cell culture solution. 600g at 4 ℃, centrifugating for 5min, and collecting cells. The supernatant was removed, lysate was added, cells were lysed in an ice bath, and the cells were centrifuged at 16,000g at 4 ℃ for 12 min. The supernatant was collected, and the protein concentration was determined and adjusted to 2 mg/mL. Configuring a reaction system according to the requirements of the specification, detecting and adding Caspase-3 chromogenic substrate Ac-DEVD-pNA (2mmol/L) by Caspase-3, and detecting and adding Caspase-9 chromogenic substrate Ac-LEHD-pNA (2mmol/L) by Caspase-9. After incubation at 37 ℃ for 100min, absorbance at 405nm was measured using a microplate reader (Thermo-electric Thermo full-automatic MK3, siemer feishel, usa). The absorbance values of the normal groups were taken as 100% with the normal groups as a reference, and the relative Caspase-3, 9 activities of the groups were expressed by the measured optical density values of the experimental group/optical density values of the normal group, respectively.
As shown in FIGS. 2 and 3, the activity of Caspase-3, 9 was significantly different from that of the group without drug (P <0.05) at a dose of 8 umol/L. 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase the activity of Caspase-3, 9. With the gradual increase of the dosage of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the activity of Caspase-3, 9 is gradually increased in a dose-dependent relationship.
Example 4
And detecting the expression of apoptosis related genes Bcl-2 and Bax mRNA in the cells by real-time fluorescence quantitative PCR. Subjecting each group of cells to 0, 2, 4, 8, 16, 32, 64 μmol/L4- (4-methylphenny) -1,3-thiazol-2-amine action for 48h, extracting total RNA in cells by Trizol method, and measuring OD by ultraviolet spectrophotometer260And OD280The absorbance, the concentration and purity of the RNA calculated, 1.8<OD260/OD280<2.2. PrimeScript Using reverse transcription kitTMRT reagent kit with gDNA Eraser (Dalibao bioengineering Co., Ltd.) reverse transcribes the extracted total RNA into cDNA. Then, the cDNA after reverse transcription was used as a template, GAPDH was used as an internal control, and Green was usedTMPremixEx TaqTMII (Tli RNaseH plus) (Dalianbao bioengineering Co., Ltd.) the fluorescent quantitation kit was used to perform fluorescent quantitation PCR amplification on a Roche LightCycler96 fluorescent quantitation PCR instrument. Prepare 20 μ L reaction system: mu.L of cDNA, 10. mu.L of TB GreenPremix Ex TaqII (2X), 0.8. mu.L of PCR Forward Primer (10. mu.M), 0.8. mu.L of PCR Reverse Primer (10. mu.M), and 6.4. mu.L of sterile deionized water. Reaction conditions are as follows: pre-denaturation at 95 ℃ for 30 s; denaturation 95 ℃ for 5s, annealing extension 60 ℃ for 20s, 35 cycles were repeated. Relative expression amounts of the respective genes 2－ΔΔCtAnd (4) showing. The experiment was repeated 3 times in total. The primer sequences are shown in Table 2:
TABLE 2 real-time fluorescent quantitation PCR primer information
Figure BDA0002683243720000091
Results as shown in figures 4 and 5, significant differences in cellular Bcl-2mRNA and Bax mRNA expression occurred from the 8 μmol/L dose compared to the drug-free group (P < 0.05). 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine can obviously increase Bax mRNA expression and reduce Bcl-2mRNA expression. With the gradual increase of the dose of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the expression of Bax mRNA is gradually increased, and the expression of Bcl-2mRNA is gradually reduced in a dose-dependent relationship.
Example 5
Solid tumors of 4- (4-vinylphenyl) -1,3-thiazol-2-amine on HCT116The effect of tumor volume and tumor suppression rate in mice. HCT116 cells were cultured at 37 ℃ in 5% CO2And (5) in a constant-temperature incubator, carrying out passage once for 2-3 d. When the cells divide exponentially, they are digested with pancreatin and washed twice with PBS to give cells with a density of 1X 107Single cell suspension per ml. A1 ml syringe is used for injecting a mouse (with the weight of (22-25) g purchased from the center of an experimental animal of Zhengzhou university, the skin under the right axilla is injected into 0.2ml of cell suspension after about 5mm, the cell suspension is injected for about 7 days, rice grain-like nodules and tough texture appear under the skin of the right axilla of the mouse, the mouse is killed after 2 weeks, the tumor is completely stripped, and the tumor weight is weighed.
The results showed that the tumor weight was less than that of the model group in both the high and low dose groups of 4- (4-vinylphenyl) -1,3-thiazol-2-amine 2 weeks after administration (FIG. 6). The differences were all statistically significant (P < 0.05). The high and low dose groups of 4- (4-vinylphenyl) -1,3-thiazol-2-amine all had higher tumor inhibition rates, with the high dose group being higher than the lower dose group (table 3).
TABLE 34 Effect of- (4-Vinylphenyl) -1,3-thiazol-2-amine on tumor weight and tumor inhibition Rate in HCT116 tumor-bearing mice
Figure BDA0002683243720000101
(Note: compare model groups*P<0.05，**P<0.01)。
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Figure BDA0002683243720000111
Figure BDA0002683243720000121
Figure BDA0002683243720000131

Claims (10)

1. A NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine with a function of treating colon cancer is characterized in that the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure FDA0002683243710000011
2. the analog 4- (4-vinylphenyl) -1,3-thiazol-2-amine according to claim 1, wherein said analog 4- (4-vinylphenyl) -1,3-thiazol-2-amine has a Compound CID of 684149 and formula C11H10N2S, molecular weight 202.28 g/mol.
3. Use of the analog 4- (4-vinylphenyl) -1,3-thiazol-2-amine according to claim 1 or 2 for the preparation of a medicament for the treatment of colon cancer.
4. Use of the analog 4- (4-vinylphenyl) -1,3-thiazol-2-amine according to claim 1 or 2 for the preparation of a medicament for inhibiting colon cancer cell proliferation.
5. Use of the analog 4- (4-vinylphenyl) -1,3-thiazol-2-amine according to claim 1 or 2 for the preparation of a medicament for promoting apoptosis of colon cancer cells.
6. The medicine for treating colon cancer is characterized in that the effective component of the medicine comprises NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure FDA0002683243710000012
7. the medicament of claim 6, wherein the medicament promotes apoptosis of colon cancer cells and inhibits proliferation of colon cancer cells.
8. An inhibitor for colon cancer cell proliferation, which is characterized in that the effective component of the medicament comprises NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure FDA0002683243710000013
9. an accelerant for colon cancer cell apoptosis is characterized in that the effective component of the medicine comprises NAT10 inhibitor analog 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine, the structure of the 4- (4-vinyl phenyl) -1, 3-thiazole-2-amine is shown as follows,
Figure FDA0002683243710000021
10. the agent of claim 9, wherein the agent reduces anti-apoptotic protein Bcl-2mRNA expression and increases pro-apoptotic protein Caspase-3, 9 content and Bax mRNA expression.
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