CN117427074A - Application of tetrahydroquinolinol as iron death inhibitor in preparation of acute kidney injury drugs - Google Patents
Application of tetrahydroquinolinol as iron death inhibitor in preparation of acute kidney injury drugs Download PDFInfo
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- CN117427074A CN117427074A CN202311514779.4A CN202311514779A CN117427074A CN 117427074 A CN117427074 A CN 117427074A CN 202311514779 A CN202311514779 A CN 202311514779A CN 117427074 A CN117427074 A CN 117427074A
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- tetrahydroquinolinol
- iron death
- pharmaceutical composition
- kidney injury
- acute kidney
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- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 229910052742 iron Inorganic materials 0.000 title claims abstract description 45
- 230000034994 death Effects 0.000 title claims abstract description 41
- JBMXELOKOJNQHV-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-2-ol Chemical compound C1=CC=C2NC(O)CCC2=C1 JBMXELOKOJNQHV-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 28
- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 25
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 25
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- 229940079593 drug Drugs 0.000 title claims abstract description 17
- 239000003112 inhibitor Substances 0.000 title claims abstract description 15
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
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- YAFQFNOUYXZVPZ-UHFFFAOYSA-N liproxstatin-1 Chemical compound ClC1=CC=CC(CNC=2C3(CCNCC3)NC3=CC=CC=C3N=2)=C1 YAFQFNOUYXZVPZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P39/00—General protective or antinoxious agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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Abstract
The application relates to the technical field of biological medicines, in particular to application of tetrahydroquinoline alcohol as an iron death inhibitor in preparation of acute kidney injury medicines. Based on the research of the action mechanism of cell iron death, the invention discovers that tetrahydroquinolinol can be used as an inhibitor for targeting cell iron death through virtual screening and cell activity test, and provides the application of the tetrahydroquinolinol in preventing and treating acute kidney injury. The tetrahydroquinolinol has a structural formula shown in formula (I), wherein the hydroxyl-substitutable sites on the benzene ring are marked as C-6, C-7 and C-8; the hydroxyl groups may form mono-substitutions at the C-6, C-7 and C-8 positions.
Description
Technical Field
The application relates to the technical field of biological medicines, in particular to application of tetrahydroquinoline alcohol as an iron death inhibitor in preparation of acute kidney injury medicines.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
Kidney disease is an important risk factor affecting human health, with kidney disease occurring in more than 10% of adults worldwide. Among them, acute Kidney Injury (AKI) is a common clinical cause of multiple organ failure, with a incidence of up to 50% in critically ill patients. Furthermore, AKI patients have a higher risk of progressing to chronic kidney disease, end stage renal disease, and up to renal failure. At present, lack of specific drugs for targeted treatment of kidney diseases is still an important reason for preventing the attack of kidney diseases, and further seriously threatens the life quality of people. Thus, prevention and treatment of acute kidney injury is a public health problem that is urgently needed to be studied.
Iron cell death (ferrovision) is a recently discovered new way of programmed cell death that differs from apoptosis, necrosis and autophagy in morphology, biochemistry and genetics. Since this process depends on the presence of iron ions, it is called iron death. The generation mechanism is as follows: the balance of intracellular membrane lipid reactive oxygen species production and degradation is deregulated and the cell undergoes iron ion dependent, oxidative, non-apoptotic programmed cell death. Typical features are: mitochondria become smaller, the density of the bilayer membrane increases, and the membrane also shows increased lipid active oxygen free radicals in the cell membrane. Recent studies have shown that iron death is an important form of cell death in a variety of acute kidney injuries.
Ferrosistatin-1 and Liproxstatin-1 are first-generation small molecule iron death inhibitors, and function to remove cell membrane lipid free radical damage and block cell iron death. The inhibitor has definite action mechanism and structure-activity relationship. However, both compounds have the disadvantage of having a short half-life and a relatively high toxicity, respectively.
Disclosure of Invention
In order to overcome the problems, the invention provides application of tetrahydroquinolinol as an iron death inhibitor in preparing acute kidney injury medicines. Based on the research of the action mechanism of cell iron death, the invention discovers that tetrahydroquinolinol can be used as an inhibitor for targeting cell iron death through cell activity test, and provides the application of the compound in preventing and treating acute kidney injury induced by kidney ischemia reperfusion.
In order to achieve the technical purpose, the invention adopts the following technical scheme:
in a first aspect of the invention, there is provided the use of tetrahydroquinolinol as an iron death inhibitor in the manufacture of a medicament for treating acute kidney injury, said tetrahydroquinolinol having the structural formula (i):
wherein, the sites which can be substituted by hydroxyl on the benzene ring are marked as C-6, C-7 and C-8; the hydroxyl groups may form mono-substitutions at the C-6, C-7 and C-8 positions.
The compounds of formula (I) include the following:
tetrahydroquinolinol can block chain reaction of membrane lipid free radical, reduce damage effect of free radical on cell membrane, prevent cell iron death, and protect cell, thereby realizing therapeutic effect on diseases related to iron death mechanism.
It should be noted that, in addition to the small molecular entity with the above structure, the tetrahydroquinolinol of the present invention also belongs to technical schemes under the same concept of the first aspect of the present invention, and belongs to technical contents of the present application protection.
Preferably, the tetrahydroquinolinol is used as an iron death inhibitor in any one of the following ways:
(1) For use in the prevention, amelioration or treatment of a disease associated with the iron death pathway;
(2) Is applied to the preparation of medicaments for preventing, improving or treating diseases related to the iron death pathway;
(3) The method is applied to the preparation of the iron death pathway inhibition model.
In the applications of the above aspects (1) and (2), the iron-death-related diseases include, but are not limited to, cancers, cerebral hemorrhage, tumors, ischemia-reperfusion injury, traumatic brain injury, parkinson's disease, plant heat stress, liver and kidney injury, biliary tract diseases, osteoarthritis, acute kidney injury, and the like; in one embodiment of the present invention, the tetrahydroquinolinols described above are used for the prevention, amelioration or treatment of acute kidney injury.
In the application of the aspect (3), the tetrahydroquinolinol is used as a model drug for preparing a basic research model, such as an iron death pathway inhibition model in HT-1080 human fibrosarcoma cells in vitro, or for inhibiting Erastin and RSL3 induced cell iron death.
In a second aspect of the invention, there is provided a pharmaceutical composition comprising an active amount of tetrahydroquinolinol as described above.
In the above pharmaceutical composition, the dosage of the compound can be adjusted conventionally according to the purpose of administration of the drug, the state of the subject, and the like. The dosage of the above compounds in the pharmaceutical composition should be an effective dose, and the pharmaceutical composition is in a dosage form that is easy to administer accurately.
When the pharmaceutical composition is applied to the preparation of a pharmaceutical formulation for in vivo administration, the pharmaceutical formulation should be sterile, and methods for achieving sterility of the pharmaceutical formulation should be known to those skilled in the art, for example, can be achieved by filtration through sterile filtration membranes, etc. Those skilled in the art can also select a suitable pharmaceutically acceptable carrier depending on the dosage form desired for the pharmaceutical composition to prepare it into a different dosage form, e.g., a gastrointestinal administration dosage form, or a parenteral administration dosage form.
Further, the above-mentioned parenteral administration type includes powder, tablet, granule, capsule, sustained-release agent, solution, dry suspension, effervescent tablet, emulsion, suspension and the like.
Further, parenteral administration includes injection administration forms (e.g., injections including intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, and intracavity injection); respiratory tract administration type (such as spray, aerosol, powder spray, etc.); skin administration forms (such as topical solutions, lotions, liniments, ointments, plasters, pastes, patches, etc., mucosal administration forms (such as eye drops, nasal drops, ophthalmic ointments, gargle, sublingual tablets, adhesive tablets, film patches, etc.), and luminal administration forms (such as suppositories, aerosols, effervescent tablets, drops, dripping pills, etc., for use in the rectum, vagina, urethra, nasal cavity, auditory canal, etc.).
Further, the medicine is injection.
In a third aspect of the present invention, there is provided the use of tetrahydroquinolinol as described above and/or a pharmaceutical composition according to the third aspect for the preparation of a medicament for use in the prevention, amelioration or treatment of acute renal injury or related.
In summary, the invention provides application of tetrahydroquinolinol in treating acute kidney injury, and in particular relates to application of the iron death inhibitor tetrahydroquinolinol in preparing a medicament for treating/relieving acute kidney injury or a supplement for preventing acute kidney injury by combined use of the iron death inhibitor tetrahydroquinolinol and the medicament.
The beneficial effects of the invention are mainly as follows: the invention provides evidence of tetrahydroquinoline alcohol in inhibiting the process of human fibrosarcoma cell HT-1080 iron death, provides a theoretical basis for treating acute kidney injury induced by kidney ischemia reperfusion with iron death as a target point, and particularly provides a basis for combined administration of the tetrahydroquinoline alcohol and an iron death inhibitor in the clinical process.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 shows that 8-hydroxy-1, 2,3, 4-tetrahydroquinoline has a significant inhibitory effect on Erastin-induced cell iron death;
FIG. 2 shows that 8-hydroxy-1, 2,3, 4-tetrahydroquinoline has a sustained inhibitory effect on RSL 3-induced iron cell death, wherein A is cell viability and B is lipid peroxidation;
FIG. 3 shows renal injury (biochemical test) in mice treated with 8-hydroxy-1, 2,3, 4-tetrahydroquinoline, wherein A is serum creatinine content and B is urea nitrogen content;
FIG. 4 shows renal injury (HE staining 40X) in 8-hydroxy-1, 2,3, 4-tetrahydroquinoline treatment mice, where a is control; b is 8-hydroxy-1, 2,3, 4-tetrahydroquinoline (40 mg/kg); c is a renal ischemia reperfusion surgery group; d is 8-hydroxy-1, 2,3, 4-tetrahydroquinoline (40 mg/kg) + renal ischemia reperfusion surgery group (500 mg/kg).
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present invention. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
In order to enable those skilled in the art to more clearly understand the technical scheme of the present invention, the technical scheme of the present invention will be described in detail with reference to specific embodiments.
The preparation of experimental raw materials:
the compound monomer 8-hydroxy-1, 2,3, 4-tetrahydroquinoline is purchased from Shanghai Jizhui Biochemical technology Co., ltd, ferrositin-1, erastin and RSL3 are purchased from sigma company, and are all dissolved in sterile dimethyl sulfoxide DMSO to prepare the required concentration.
Culture of HT-1080 human fibrosarcoma cells:
HT-1080 human fibrosarcoma cell line culture conditions: DMEM high sugar medium (GIBCO) containing 10% FBS (GIBCO), 37 ℃,5% co 2 Saturated humidity incubator.
Statistics used in the present invention were analyzed using R software and experimental data were expressed as mean±sem. The comparison between the groups of cells and animals was tested using Tukey's test (ANOVA), the comparison between the two groups was tested using Student's t-test, and was considered statistically significant by P <0.05, with the letter differences representing P <0.05.
Experimental example 1 8-hydroxy-1, 2,3, 4-tetrahydroquinoline inhibiting Erastin-induced iron death
After adherence of cultured HT-1080 human fibrosarcoma cells, DMSO, erastin (10. Mu.M, final concentration), erastin (10. Mu.M) +8-hydroxy-1, 2,3, 4-tetrahydroquinoline (1. Mu.M), erastin (10. Mu.M) +Ferrostatin-1 (0.1. Mu.M) were added to the medium, respectively. Cell viability was measured by MTT 24 hours after treatment and the experiment was repeated 3 times. The final cell viability results are shown in figure 1 (data obtained after 3 replicates of the experiment).
Cell viability assay (MTT): HT-1080 cells treated with drug for 24 hours were assayed for cell viability by MTT colorimetric assay, the MTT kit being available from Beijing Soy Bao technology Co.
As shown in fig. 1, compared with the control group, the iron death inducer Erastin stimulation can significantly kill cells; 8-hydroxy-1, 2,3, 4-tetrahydroquinoline can obviously inhibit cell death induced by Erastin (p < 0.01), and the activity is equivalent to that of positive control Ferrositin-1. 8-hydroxy-1, 2,3, 4-tetrahydroquinoline is shown to have a significant inhibition of Erastin-induced cell iron death.
Experimental example 2 8-hydroxy-1, 2,3, 4-tetrahydroquinoline inhibiting RSL 3-induced iron death
After adherence of cultured HT-1080 human fibrosarcoma cells, DMSO, RSL3 (3. Mu.M, final concentration), RSL3 (3. Mu.M) +8-hydroxy-1, 2,3, 4-tetrahydroquinoline (1. Mu.M), RSL3 (3. Mu.M) +Ferrostatin-1 (0.1. Mu.M) were added to the medium, respectively. Cell viability and cell membrane lipid peroxidation level were measured by MTT 24 hours after treatment, the experiment was repeated 3 times, the survival rate results of the final cells are shown in fig. 2 a (data obtained after 3 times of experiment), the cell membrane lipid peroxidation level, and the final inhibitory effect is shown in fig. 2B (data obtained after 3 times of experiment).
Cell viability assay (MTT): HT-1080 cells treated with drug for 24 hours were assayed for cell viability by MTT colorimetric assay, the MTT kit being available from Beijing Soy Bao technology Co. Cell membrane lipid peroxidation level assay: HT-1080 cells after 12 hours of drug addition were digested with pancreatin into single cell suspensions. C11-BODIPY (10. Mu.M) was incubated for 30 min at room temperature in the absence of light, washed 3 times with PBS, and examined by flow cytometry, and C11-BODIPY was purchased from a thermosher.
The experimental results show that: as shown in fig. 2 a, the iron death inducer RSL3 stimulation significantly killed the cells compared to the control group; whereas 8-hydroxy-1, 2,3, 4-tetrahydroquinoline significantly inhibited RSL 3-induced cell death (p < 0.01), and the activity was comparable to that of positive control Ferrostatin-1. Meanwhile, as shown in fig. 2B, 8-hydroxy-1, 2,3, 4-tetrahydroquinoline can significantly scavenge RSL 3-induced lipid radicals (p < 0.01). 8-hydroxy-1, 2,3, 4-tetrahydroquinoline was shown to have a significant inhibition of RSL-3 induced cellular iron death.
Experimental example 3 8-hydroxy-1, 2,3, 4-tetrahydroquinoline for alleviating acute renal injury in mice induced by renal ischemia reperfusion
Renal ischemia reperfusion is commonly used to create models of acute kidney injury, in which mice are treated with renal ischemia reperfusion surgery to achieve the effects of acute kidney injury, and stimulation of renal ischemia reperfusion causes necrosis and apoptosis of the mouse kidney cells, with elevated Serum Creatinine (SC) and urea nitrogen (BUN) levels, and massive inflammatory cell infiltration into the kidney.
Grouping animals: 40C 57BL/6Nj mice with the age of 8-10 weeks are selected and purchased from Experimental animal science and technology limited company of Beijing, the 40 mice are randomly divided into the following 4 groups, namely, male and female mice are randomly divided into control groups; a renal ischemia reperfusion surgery group; 8-hydroxy-1, 2,3, 4-tetrahydroquinoline (40 mg/kg); 8-hydroxy-1, 2,3, 4-tetrahydroquinoline (40 mg/kg) + renal ischemia reperfusion surgery group (500 mg/kg).
Treatment of animals: the acute kidney injury model of the mice is induced by kidney ischemia reperfusion, the mice are clamped on two side kidney pedicles through two side lumbar vertebra outer side incisions for 45 minutes, the incisions are closed after the clamping is taken down, blood flow is recovered, standard feed is fed, and kidney ischemia reperfusion injury test is carried out. The body temperature is kept between 36 and 37 ℃ during the whole operation. All ischemia reperfusion experiments were performed using the double blind method. 8-hydroxy-1, 2,3, 4-tetrahydroquinoline (40 mg/kg) was injected intraperitoneally twice 24 hours and 1 hour before ischemia occurred, respectively. Mice were sacrificed 24h after reperfusion and blood samples were collected from the retroorbital venous plexus for renal function testing. The mice were then dissected and immediately kidney tissue was removed for subsequent conventional HE staining, the results are shown in fig. 4.
Renal function detection: and (3) standing the collected whole blood of each group of mice for 1-2 hours, directly centrifuging at a low speed to separate serum for later use, diluting the separated serum sample by 5 times, and operating the sample according to the specifications of Serum Creatinine (SC) and urea nitrogen (BUN) detection kit products respectively. Serum creatinine and urea assays were performed at the Shandong university of first medical science and the results are shown in FIG. 3.
As shown in FIG. 3, the content of SC and BUN in serum of the 8-hydroxy-1, 2,3, 4-tetrahydroquinoline treatment group is obviously reduced, and as shown in FIG. 4, the necrosis area of the 8-hydroxy-1, 2,3, 4-tetrahydroquinoline treatment group is obviously reduced compared with that of the renal ischemia reperfusion treatment group, so that the 8-hydroxy-1, 2,3, 4-tetrahydroquinoline has the effect of relieving acute drug-induced renal injury of mice induced by renal ischemia reperfusion.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. The application of tetrahydroquinolinol as an iron death inhibitor in preparing acute kidney injury medicines is characterized in that the tetrahydroquinolinol has a structural formula shown in a formula (I):
wherein, the sites which can be substituted by hydroxyl on the benzene ring are marked as C-6, C-7 and C-8; the hydroxyl groups may form mono-substitutions at the C-6, C-7 and C-8 positions.
2. The use of claim 1, further comprising hydrates, solvates, pharmaceutically acceptable salts and pharmaceutically acceptable esters of said tetrahydroquinolinols.
3. The use according to claim 1, wherein the tetrahydroquinolinol is used in any of the following ways:
(1) For use in the prevention, amelioration or treatment of a disease associated with the iron death pathway;
(2) Is applied to the preparation of medicaments for preventing, improving or treating diseases related to the iron death pathway;
(3) The method is applied to the preparation of the iron death pathway inhibition model.
4. The use according to claim 3, wherein in the use of aspects (1) and (2), the iron death-related diseases include, but are not limited to, cancer, cerebral hemorrhage, tumor, ischemia-reperfusion injury, traumatic brain injury, parkinson's disease, plant heat stress, liver and kidney injury, biliary tract disease, osteoarthritis, acute kidney injury; preferably, the tetrahydroquinolinol is used for preventing, ameliorating or treating acute kidney injury.
5. The use according to claim 3, wherein in the use of aspect (3), the tetrahydroquinolinol is used as a model drug in the preparation of a model of basic research, such as an iron death pathway inhibition model in HT-1080 human fibrosarcoma cells in vitro, or for inhibiting iron death in cells induced by Erastin and RSL 3.
6. A pharmaceutical composition comprising an active amount of tetrahydroquinolinol as in claim 1.
7. The pharmaceutical composition of claim 6, wherein the dosage of tetrahydroquinolinol is an effective dosage and the pharmaceutical composition is in a dosage form that is easy to administer accurately.
8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is sterile when applied in preparing a pharmaceutical formulation for in vivo administration; the pharmaceutical composition also comprises a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 6, wherein the dosage form comprises a gastrointestinal dosage form, or a parenteral dosage form;
the gastrointestinal tract administration type preparation comprises powder, tablets, granules, capsules, sustained release agents, solutions, dry suspensions, effervescent tablets, emulsions and suspensions;
the parenteral administration form includes injection administration form, respiratory tract administration form, skin administration form; a mucosal dosage form, a luminal dosage form;
preferably, the above-mentioned drugs are in the form of injectable administration.
10. Use of tetrahydroquinolinol as claimed in claim 1 and/or a pharmaceutical composition as claimed in claim 6 for the preparation of a medicament for the prevention, amelioration or treatment of acute kidney injury or related.
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