CN116570589A - Application of Compound Parimifasor in the Preparation of Antitumor Drugs - Google Patents

Abstract

The invention discloses an application of a compound Parimiferator in preparing an anti-tumor drug, belonging to the field of medicines. According to the invention, through in vitro anti-tumor experiments, the compound Parimiferator has broad-spectrum anti-tumor activity, and has strong inhibition activity on human glioblastoma (LN 229), colon cancer (HCT-116), lung adenocarcinoma (H1299), large cell lung cancer (NCI-H460), renal clear cell carcinoma (786-O), osteosarcoma (143B), esophageal cancer (KYSE 140), pancreatic cancer (PANC-1), cholangiocellular carcinoma (HCCC-9810), cervical cancer (Hela), hepatocellular carcinoma (HepG 2), fibrosarcoma (HT-1080), gastric cancer (HGC-27), bladder transitional cell carcinoma (UM-UC-3) and melanoma (A375) cell lines, and is hopeful to be developed into a novel broad-spectrum anti-tumor medicament.

Description

Application of Compound Parimifasor in the Preparation of Antitumor Drugs

technical field

The invention belongs to the field of medicine, and in particular relates to the application of a compound Parimifasor in the preparation of antitumor drugs.

Background technique

Malignant tumor is one of the main causes of death of patients, and its incidence is increasing year by year, and the patients are getting younger and younger, which seriously threatens human health and imposes a huge burden on the country and society. At present, tumor treatment measures mainly include surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy. In the clinical treatment of tumors, a combination of different treatment options and drugs is often required. Therefore, continuous exploration of potential tumor therapeutic drugs is an important issue that needs to be solved urgently, and it also provides more possibilities for cancer patients.

The compound Parimifasor is an immunomodulator with anti-inflammatory activity. There haven't been any studies on parimifasor and tumors.

Contents of the invention

In order to make up for the deficiencies of the prior art, the present invention provides an application of the compound Parimifasor in the preparation of antitumor drugs.

Compound Parimifasor structural formula of the present invention is as follows:

The results of in vitro anti-tumor activity screening showed that the compound Parimifasor had broad-spectrum anti-tumor activity, and it was effective against human glioblastoma (LN229), colon cancer (HCT-116), lung adenocarcinoma (H1299), large cell lung cancer (NCI -H460), clear cell renal cell carcinoma (786-O), osteosarcoma (143B), esophageal cancer (KYSE140), pancreatic cancer (PANC-1), cholangiocarcinoma (HCCC-9810), cervical cancer (Hela), Hepatocellular carcinoma (HepG2), fibrosarcoma (HT-1080), gastric carcinoma (HGC-27), bladder transitional cell carcinoma (UM-UC-3) and melanoma (A375) cell lines all showed strong inhibitory activity, Its _IC50 values are 0.07μM, 0.19μM, 0.30μM, 3.24μM, 0.43μM, 0.68μM, 0.23μM, 0.24μM, 0.41μM, 0.14μM, 1.67μM, 0.29μM, 1.30μM, 0.63μM, 0.21μM . Therefore, the compound Parimifasor or a pharmaceutically acceptable salt thereof has application in the preparation of anti-tumor drugs, more specifically, the anti-tumor drugs are at least one of the following drugs: treatment of anti-glioblastoma Drugs, anti-colon cancer drugs, anti-lung adenocarcinoma drugs, anti-large cell lung cancer drugs, anti-renal clear cell carcinoma drugs, anti-osteosarcoma drugs, anti-esophageal cancer drugs, anti-pancreatic cancer drugs, anti-cholangiocarcinoma drugs, anti-cervical cancer drugs Cancer drugs, anti-hepatocellular carcinoma drugs, anti-fibrosarcoma drugs, anti-gastric cancer drugs, anti-bladder transitional cell carcinoma drugs, anti-melanoma drugs.

The antitumor drug comprises effective dosage of Parimifasor or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable carriers, excipients and/or auxiliary materials.

Pharmaceutically acceptable carriers are various carriers known in the art, and are prepared according to methods known in the art. For example: diluents, excipients such as water, etc.; binders such as cellulose derivatives, gelatin, polyvinylpyrrolidone, etc.; fillers such as starch, etc.; disintegrating agents such as calcium carbonate, sodium bicarbonate, etc.

Pharmaceutically acceptable excipients include various excipients commonly used in this field, such as sweeteners, buffers, co-solvents, colorants, fragrances or other materials.

The compound Parimifasor or a pharmaceutically acceptable salt thereof can be combined with one or more solid and/or liquid pharmaceutical excipients and/or auxiliary materials to prepare a suitable use form or dosage form for human medicine.

The antitumor drug can be prepared in various dosage forms, such as tablets, capsules, pills, injections, sustained-release preparations or controlled-release preparations.

The present invention has the following beneficial effects: the present invention finds that the compound Parimifasor has good antitumor activity on 15 different types of tumor cell lines through in vitro antitumor tests, and it can be used to prepare broad-spectrum antitumor drugs, with Good development prospects.

Detailed ways

Below in conjunction with embodiment the present invention is described in further detail. The following examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

Example 1

1. Experimental method

1. Cell Culture

When the cell confluency reaches 80-90%, subculture is carried out. When subculture, remove the original medium, wash the cells with an appropriate amount of PBS, and then digest with 0.25% trypsin. At the end of the digestion, use 5 times the volume of trypsin for complete culture After the centrifugation was completed, the supernatant was discarded, and the cells were resuspended with 1 mL of fresh medium, and the cells were transferred to a new culture dish in an appropriate proportion, and put Cultured in a 37°C, 5% CO ₂ incubator.

2. Compound working solution preparation

First dilute the compound Parimifasor stock solution with DMSO to 500 times the highest concentration required for each cell, then add 2 μL of the above compound dilution to 298 μL complete medium to obtain 10/3× working solution W1, and then use 1/150 ( v/v) The DMSO medium was serially diluted according to the dilution ratio set for each cell to obtain the working solution W2-9, and finally the DMSO content of all wells was uniformly controlled at 0.2%.

3. Cell inoculation and drug treatment

Collect the cells in the logarithmic growth phase, resuspend them with complete medium, inoculate the cells into 96-well plates at 70 μL per well, (plating density HCT-116: 3200 cells/well; KYSE140: 16000 cells/well; Hela: 1800 pcs/well; A375: 1600 pcs/well; PANC-1: 3200 pcs/well; H1299: 2500 pcs/well; LN229: 2400 pcs/well; HepG2: 6000 pcs/well; 786-O: 3000 pcs/well ; NCI-H460: 14000 cells/well; HCCC-9810: 1500 cells/well; 143B: 1600 cells/well; ) adhere to the wall overnight in a 37°C, 5% CO ₂ incubator. After the cells were completely adhered to the wall, 30 μL of the corresponding 2× compound working solution was added to each well, and the incubation was continued for 72 hours. 9 concentration points were set for each compound, and 3 replicate wells were set for all groups. The medium well without cells was used as the blank control, and the cell culture well only added with the solvent was used as the negative control.

4. Cell proliferation detection and data processing

After the incubation, add 10 μL of CCK8 solution to each well, continue to incubate for 2-4 hours, and then measure the absorbance value at 450 nm on a microplate reader. % inhibition rate=(1-(OD _S -OD _BLK )/(OD _NC -OD _BLK ))×100%. Among them, OD _S indicates the absorbance value of the sample well (cell + test compound), OD _NC indicates the absorbance value of the negative well (cell + vehicle), and OD _BLK indicates the absorbance value of the blank well (medium + vehicle). The dose-effect curve was fitted using PRISM software, and the IC ₅₀ value was calculated.

2. Experimental results

Table 1 shows the results of the antitumor activity of the compound Parimifasor on 15 tumor cell lines.

The in vitro antitumor activity of table 1 compound Parimifasor

It can be seen from Table ₁ that the compound Parimifasor has broad-spectrum anti-tumor activity, and has a strong inhibitory effect on the proliferation of all tumor cell lines. _{The 50} is less than 1 μM, and the IC ₅₀ of 10 tumor cell lines is less than 0.5 μM. Therefore, the compound Parimifasor is expected to be developed into a new broad-spectrum antitumor drug.

Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention, and any person skilled in the art can use the methods disclosed above and technical content to analyze the present invention without departing from the spirit and scope of the present invention. Possible changes and modifications are made in the technical solution. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention, which do not depart from the content of the technical solution of the present invention, all belong to the technical solution of the present invention. protected range.

Claims (7)

1. The application of the compound Parimiferator or pharmaceutically acceptable salt thereof in preparing antitumor drugs is characterized in that: the structural formula of the compound Parimiferator is shown as the formula (I):

2. the use according to claim 1, characterized in that: the antitumor drug is at least one of the following drugs: therapeutic anti-glioblastoma drugs, anti-colon cancer drugs, anti-lung adenocarcinoma drugs, anti-large cell lung cancer drugs, anti-renal clear cell carcinoma drugs, anti-osteosarcoma drugs, anti-esophageal cancer drugs, anti-pancreatic cancer drugs, anti-cholangiocyte type liver cancer drugs, anti-cervical cancer drugs, anti-hepatocellular carcinoma drugs, anti-fibrosarcoma drugs, anti-gastric cancer drugs, anti-bladder transitional cell carcinoma drugs, anti-melanoma drugs.

3. The use according to claim 1, characterized in that: the antitumor drug comprises an effective dose of Parimiferasor or pharmaceutically acceptable salt thereof.

4. A use according to claim 3, characterized in that: the antitumor drug also comprises a pharmaceutically acceptable carrier, an excipient and/or an auxiliary material.

5. The use according to claim 1, characterized in that: the dosage form of the antitumor drug is tablets, capsules, pills, injections, sustained release preparations or controlled release preparations.

6. A pharmaceutical composition characterized by: comprises a pharmaceutically effective amount of a compound Parimiferator with a structural formula shown as a formula (I) or pharmaceutically acceptable salt thereof.

7. The pharmaceutical composition according to claim 6, wherein: and also comprises pharmaceutically acceptable carriers, excipients and/or auxiliary materials.