CN116570589A - Application of compound Parimiferator in preparation of antitumor drugs - Google Patents
Application of compound Parimiferator in preparation of antitumor drugs Download PDFInfo
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- CN116570589A CN116570589A CN202310619499.3A CN202310619499A CN116570589A CN 116570589 A CN116570589 A CN 116570589A CN 202310619499 A CN202310619499 A CN 202310619499A CN 116570589 A CN116570589 A CN 116570589A
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- 206010008342 Cervix carcinoma Diseases 0.000 claims abstract description 4
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Classifications
-
- 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
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
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
Technical Field
The invention belongs to the field of medicines, and particularly relates to an application of a compound Parimiferator in preparation of antitumor drugs.
Background
Malignant tumor is one of the most main causes of death of patients, and the incidence rate of malignant tumor is in an annual rising trend, so that the sick people are more and more younger, the human health is seriously threatened, and great burden is also caused to the country and the society. At present, tumor treatment measures mainly comprise operation treatment, radiotherapy, chemotherapy, targeted treatment, immunotherapy and the like. In the clinical treatment of tumors, combinations of different treatment regimens and drugs are often required. Therefore, the continuous development of potential tumor therapeutic drugs is an important topic to be solved urgently, and provides more possibilities for tumor patients.
The compound Parimiferator is an immunomodulator and has anti-inflammatory activity. There is no current study on Parimiferator and tumors.
Disclosure of Invention
In order to make up the defects of the prior art, the invention provides application of a compound Parimiferator in preparing antitumor drugs.
The structural formula of the compound Parimiferator is shown as follows:
the in vitro anti-tumor activity screening result shows that 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), transitional cell carcinoma of the bladder (UM-UC-3) and melanoma (A375) cell lines, and IC thereof 50 The values were 0.07. Mu.M, 0.19. Mu.M, 0.30. Mu.M, 3.24. Mu.M, 0.43. Mu.M, 0.68. Mu.M, 0.23. Mu.M, 0.24. Mu.M, 0.41. Mu.M, 0.14. Mu.M, 1.67. Mu.M, 0.29. Mu.M, 1.30. Mu.M, 0.63. Mu.M, and 0.21. Mu.M, respectively. Therefore, the compound Parimiferator or the pharmaceutically acceptable salt thereof has application in preparing anti-tumor drugs, more specifically, the anti-tumor drugs are 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 drugsA medicament, an anti-transitional cell carcinoma medicament, and an anti-melanoma medicament.
The antitumor drug comprises an effective dose of Parimiferator or pharmaceutically acceptable salt thereof, and pharmaceutically acceptable carriers, excipients and/or auxiliary materials.
Pharmaceutically acceptable carriers are various carriers well known in the art and are prepared according to methods well known in the art. For example: diluents, excipients such as water, and the like; binders such as cellulose derivatives, gelatin, polyvinylpyrrolidone, and the like; fillers such as starch and the like; and disintegrating agents such as calcium carbonate, sodium bicarbonate, etc.
Pharmaceutically acceptable excipients include various excipients conventionally used in the art, such as sweeteners, buffers, co-solvents, coloring agents, flavors or other materials.
The compound Parimiferator or the pharmaceutically acceptable salt thereof can be combined with one or more solid and/or liquid pharmaceutical excipients and/or auxiliary materials to prepare a proper use form or dosage form for human medicine.
The antitumor drug can be prepared into preparations with various dosage forms, such as tablets, capsules, pills, injections, sustained release preparations or controlled release preparations.
The invention has the following beneficial effects: the invention discovers that the compound Parimiferator has better anti-tumor activity on 15 different types of tumor cell lines through in vitro anti-tumor experiments, can be used for preparing broad-spectrum anti-tumor drugs, and has good development prospect.
Detailed Description
The present invention will be described in further detail with reference to examples. The following examples are only illustrative of the present invention and are not intended to limit the scope of the invention.
Example 1
1. Experimental method
1. Cell culture
When the cell confluency reaches 80-90%, the cells are passaged, when passaged, the original culture medium is removed, the cells are washed by a proper amount of PBS, then are digested by 0.25% pancreatin, and at the end of the digestion, the cells are digested by 5 times of pancreatinThe complete medium volume was stopped from digestion, cells were collected, centrifuged at 200g for 5 min, after centrifugation was completed, the supernatant was discarded, the cells were resuspended in 1mL fresh medium and transferred to a fresh dish in the appropriate proportions, placed at 37℃in 5% CO 2 Culturing in an incubator.
2. Preparation of compound working solution
Firstly, diluting a compound Pariminaror stock solution to 500 times of the highest concentration required by each cell by using DMSO, then adding 2 mu L of the compound diluent into 298 mu L of complete culture medium to obtain 10/3 Xworking solution W1, then carrying out gradient dilution by using culture medium containing 1/150 (v/v) DMSO according to the dilution ratio set by each cell to obtain working solution W2-9, and finally uniformly controlling the DMSO content of all wells to be 0.2%.
3. Cell seeding and drug treatment
Cells in the logarithmic phase were collected and resuspended in complete medium and plated in 96-well plates at 70. Mu.L per well (plating density HCT-116: 3200/well; KYSE140: 16000/well; hela: 1800/well; A375: 1600/well; PANC-1: 3200/well; H1299: 2500/well; LN229: 2400/well; hepG2: 6000/well; 786-O: 3000/well; NCI-H460: 14000/well; HCCC-9810: 1500/well; 143B: 1600/well;) at 37℃with 5% CO) 2 The incubator was allowed to adhere overnight. After cell attachment was complete, 30 μl of the corresponding 2 x compound working solution was added to each well and incubation was continued for 72 hours. All compounds were set at 9 concentration points each and all groups were set at 3 duplicate wells. Cell-free medium wells served as blank control and cell culture wells with vehicle alone served as negative control.
4. Cell proliferation assay and data processing
After the incubation was completed, 10. Mu.L of CCK8 solution was added to each well and incubation was continued for 2-4 hours, followed by measurement of absorbance at 450nm on a microplate reader. % inhibition = (1- (OD) S -OD BLK )/(OD NC –OD BLK ) X 100%. Wherein OD S Represents absorbance (cell + test compound), OD of sample well NC Represents negative Kong Xiguang value (cell+vehicle), OD BLK Represent blank Kong XiguangValues (medium + vehicle). Quantity-effect curve fitting was performed using PRISM software and IC was calculated 50 Values.
2. Experimental results
The results of the antitumor activity assay of the compound Parimiferator on 15 tumor cell lines are shown in Table 1.
In vitro anti-tumor Activity of Parimiferator, a Compound of Table 1
As can be seen from Table 1, the compound Parimiferator has broad-spectrum anti-tumor activity, and has strong inhibition effect on proliferation of all tumor cell lines, and IC thereof 50 Distributed in the range of 0.07-3.24. Mu.M, with IC of 12 tumor cell lines 50 Less than 1. Mu.M, IC of 10 tumor cell lines 50 Less than 0.5 μm. Therefore, the compound Parimiferator is hopeful to be developed into a novel broad-spectrum antitumor drug.
Although the present invention has been described in terms of the preferred embodiments, it is not intended to be limited to the embodiments, and any person skilled in the art can make any possible variations and modifications to the technical solution of the present invention by using the methods and technical matters disclosed above without departing from the spirit and scope of the present invention, so any simple modifications, equivalent variations and modifications to the embodiments described above according to the technical matters of the present invention are within the scope of the technical matters of the present invention.
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310619499.3A CN116570589A (en) | 2023-05-30 | 2023-05-30 | Application of compound Parimiferator in preparation of antitumor drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310619499.3A CN116570589A (en) | 2023-05-30 | 2023-05-30 | Application of compound Parimiferator in preparation of antitumor drugs |
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| CN116570589A true CN116570589A (en) | 2023-08-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310619499.3A Pending CN116570589A (en) | 2023-05-30 | 2023-05-30 | Application of compound Parimiferator in preparation of antitumor drugs |
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| Country | Link |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117482086A (en) * | 2023-12-11 | 2024-02-02 | 上海交通大学医学院 | Application of drug small molecule Parimiferator in preparation of anti-novel coronavirus drug |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105899489A (en) * | 2013-12-10 | 2016-08-24 | 莱斯拉公司 | Trifluoromethyl pyrazolyl guanidine F1FO-ATPase inhibitors and therapeutic uses thereof |
| US20160304465A1 (en) * | 2013-12-10 | 2016-10-20 | Lycera Corporation | Alkylpyrazolyl guanidine f1f0-atpase inhibitors and therapeutic uses thereof |
| CN108486117A (en) * | 2018-04-27 | 2018-09-04 | 浙江大学 | A kind of RNA inhibitor and its application in inhibiting F1F0-ATP synthase activities |
| CN114686461A (en) * | 2022-04-08 | 2022-07-01 | 南阳理工学院 | Application of deubiquitinase USP45 in preparation of lung squamous carcinoma treatment drug |
| CN114728170A (en) * | 2019-12-20 | 2022-07-08 | 纽韦卢森公司 | Compounds active on nuclear receptors |
-
2023
- 2023-05-30 CN CN202310619499.3A patent/CN116570589A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105899489A (en) * | 2013-12-10 | 2016-08-24 | 莱斯拉公司 | Trifluoromethyl pyrazolyl guanidine F1FO-ATPase inhibitors and therapeutic uses thereof |
| US20160304465A1 (en) * | 2013-12-10 | 2016-10-20 | Lycera Corporation | Alkylpyrazolyl guanidine f1f0-atpase inhibitors and therapeutic uses thereof |
| CN108486117A (en) * | 2018-04-27 | 2018-09-04 | 浙江大学 | A kind of RNA inhibitor and its application in inhibiting F1F0-ATP synthase activities |
| CN114728170A (en) * | 2019-12-20 | 2022-07-08 | 纽韦卢森公司 | Compounds active on nuclear receptors |
| CN114686461A (en) * | 2022-04-08 | 2022-07-01 | 南阳理工学院 | Application of deubiquitinase USP45 in preparation of lung squamous carcinoma treatment drug |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117482086A (en) * | 2023-12-11 | 2024-02-02 | 上海交通大学医学院 | Application of drug small molecule Parimiferator in preparation of anti-novel coronavirus drug |
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