CN115317480B - Pharmaceutical use of N- (3-methyl-5-isothiazolyl) -2-oxo-3- (2H) -benzoxazole acetamide - Google Patents
Pharmaceutical use of N- (3-methyl-5-isothiazolyl) -2-oxo-3- (2H) -benzoxazole acetamide Download PDFInfo
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- CN115317480B CN115317480B CN202211070877.9A CN202211070877A CN115317480B CN 115317480 B CN115317480 B CN 115317480B CN 202211070877 A CN202211070877 A CN 202211070877A CN 115317480 B CN115317480 B CN 115317480B
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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
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Abstract
The invention belongs to the technical field of medicines, discloses a medicinal application of N- (3-methyl-5-isothiazolyl) -2-oxo-3- (2H) -benzoxazole acetamide, and relates to an application thereof in preparing a medicine for preventing and treating Alzheimer disease. The invention screens out a naturally occurring FoxO1 agonist by computer-aided technology, and verifies the regulatory capacity of the compound for FoxO1 by a series of downstream biological experiments. Expression of FoxO1 downstream genes P21, BIM and PPARgamma can be up-regulated, and Aβ production can be reduced by inhibiting BACE1 activity. Therefore, the preparation method can be used for preparing the Alzheimer disease prevention and treatment medicine. The structural formula of the compound is shown in the specification,
。
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an application of N- (3-methyl-5-isothiazolyl) -2-oxo-3- (2H) -benzoxazole acetamide in preparation of Alzheimer disease prevention and treatment medicines.
Background
Alzheimer's Disease (AD) is also known as senile dementia, and is a progressive, persistent neurodegenerative disease that destroys cognitive and memory functions. Its main pathological characteristics are mainly deposition of beta amyloid protein (Abeta) and neurofibrillary tangles (neurofibrillary tangle, NFT) formed by hyperphosphorylation of Tau protein. AD patients manifest as reduced voluntary behavioural ability, loss of cognitive ability, such as memory and language disorders, behavioural disorders and mood disorders. About 990 ten thousand new cases of dementia are diagnosed each year as reported by the world health organization. It is predicted that by 2032, the total number of dementia patients will be approximately 7500 ten thousand. Treatment of AD has been a hot topic in the areas of drug discovery and clinical research for the last 20 years.
Currently, drugs for the treatment of AD are cholinesterase inhibitor 5 and (N-methyl-D-aspartic acid) NMDA receptor antagonists. Unfortunately, these drugs only alleviate the symptoms of AD, but do not reverse the pathological processes of AD. The brain tissue of the patient suffering from AD has obvious atrophy, and senile plaques formed by beta amyloid (Abeta) deposition are visible at the parts, so that the senile plaques are key factors for the development of AD. In recent years, many studies have shown that both the neurochemical and neuropathological changes of AD are closely related to aβ, and that aβ proteins aggregate into polymers with high neurotoxicity and cause the body to produce factors inducing neuronal death such as oxidative stress, inflammation and high phosphorylation of Tau protein when aβ is produced too much or cleared less. Thus, aβ is the most important pathological factor in the pathogenesis of AD, and drug treatment strategies based on the amyloid cascade hypothesis may reduce the levels of aβ, which may be relevant for the treatment of AD. Therefore, the search for new drugs is rising.
FoxO1 is the most important transcription factor in FoxO family, and plays an important role in regulating cell proliferation, oxidative stress, cerebral ischemia, autophagy, neurodegenerative diseases, etc. FoxO1 may be a potential target for the treatment of AD. However, to date, there are no FoxO1 agonists for the treatment of AD.
Disclosure of Invention
The invention aims to provide an application of N- (3-methyl-5-isothiazolyl) -2-oxo-3- (2H) -benzoxazole acetamide in preparing a medicine for preventing and treating Alzheimer disease.
The compound is abbreviated as a compound D, and the structural formula of the compound D is shown as follows:
the ability of the compound to modulate FoxO1 was verified by a series of downstream biological experiments. The compound D is found to be a FoxO1 agonist and can up-regulate the transcription activity of a gene downstream of the FoxO 1. Meanwhile, it was found that compound D can inhibit BACE1 activity and can reduce Abeta production in SH-SY5Y cells in an in vitro cell experiment system. Therefore, the compound D can be used for preparing the Alzheimer disease prevention and treatment medicine.
The invention has the advantages that: the natural compound D of the FoxO1 is discovered through a computer-aided drug design technology, and the in vitro biological experiment proves that the molecule is a natural agonist of the FoxO 1; in human cell lines, compound D was demonstrated to act as a FoxO1 agonist, inhibiting BACE1 activity and reducing aβ production. Has the value of developing medicines for preventing and treating Alzheimer disease.
Drawings
FIG. 1 shows the molecular docking results of compound D of the present invention with FoxO 1.
FIG. 2 shows the results of molecular dynamics simulation of the compound D and FoxO1 complexes of the present invention.
FIG. 3 shows the effect of different doses of Compound D according to the invention on SH-SY5Y cell viability.
FIG. 4 shows that compound D of the present invention can increase the transcriptional activity of FoxO1 downstream related genes.
FIG. 5 shows the result of reducing Aβ production in SH-SY5Y cells by Compound D of the invention.
FIG. 6 shows that compound D of the present invention reduces Aβ production by inhibiting BACE1 activity.
Detailed Description
In previous studies, the inventors have found that the transcription factor FoxO1 may play a regulatory role in the pathogenesis of AD. Compared with the currently developed medicines, the FoxO1 has the advantage that the FoxO1 is the most important transcription factor in the FoxO family and plays an important role in regulating cell proliferation, oxidative stress, cerebral ischemia, autophagy, neurodegenerative diseases and the like. FoxO1 is expressed in different brain regions, especially in the hippocampal and cortical regions. The inventors found that FoxO1 expressed significantly lower in cortical tissue than in wild-type mice at 6 months of age in APP/PS1 transgenic mice. Overexpression of FoxO1 in AD cell models can effectively reduce aβ and Tau protein hyperphosphorylation levels. These results indicate that FoxO1 may be a potential drug target for the treatment of AD.
The pharmacological action of the compound D of the invention on AD treatment belongs to the category of first in class, but not to the category of me to or me better.
The following examples further illustrate the invention but are not to be construed as limiting the invention. Modifications and substitutions to the method, steps or conditions of the invention without departing from the spirit and nature of the invention are intended to be within the scope of the invention. The technical means used in the examples are conventional means well known to those skilled in the art unless otherwise indicated.
Example 1
1. FoxO1 protein preparation was performed using AutoDock Vina software. From the molecular docking result of fig. 1, it is shown that the compound D can have better binding with FoxO1, the main binding force is hydrogen bond, and the docking energy is: 7.9Kcal/mol, suggesting that the small molecule has better binding.
2. Molecular dynamics simulation experiments were performed using GROMACS. From the results of the RMSD, RMSF and Rg diagrams of fig. 2, it can be seen that the compound D and FoxO1 complex remain stable during 50ns simulation, which indicates that the compound D is stable and reliable, foxO1 can be effectively targeted, and the whole complex system structure is stable.
3. SH-SY5Y cells were grown at 1.5X10 per well 4 Culturing in 96-well plate for 24 hr, and replacing culture solution containing compound D in different concentration to continue culturing cells. After 24h, CCK-8 cytotoxicity assays were performed.
As can be seen from the results of FIG. 3, the cell density after treatment with Compound D was observed under a microscope, and the results were consistent with the results of CCK-8 detection. After 24 hours of the 80 mu M and 100 mu M drug action, SH-SY5Y cells have obvious apoptosis symptoms such as obvious nuclear aggregation, fragmentation and the like, and after 24 hours of the 20, 40, 60, 80 and 100 mu M drug action, the SH-SY5Y cell numbers are sequentially reduced, which shows that after 24 hours of the compound D action, the SH-SY5Y cell activity reduction has concentration dependence. The effect of varying concentrations of Compound D on SH-SY5Y cell viability was examined with CCK-8. The cell viability of SH-SY5Y cells treated with compound D gradually decreased with increasing concentration compared to the control group.
4. The effect of compound D on FoxO1 activity was further verified. Western Blot and RT-qPCR results show that compound D was found to enhance the transcriptional activity of the FoxO1 downstream target protein. With increasing concentration of compound D, protein expression levels and nucleic acid transcription levels of FoxO1 downstream genes P21, BIM and pparγ were both significantly increased, but did not cause an increase in FoxO1 protein expression levels. As shown in fig. 4, the protein expression levels of P21 and BIM gradually increased with increasing concentration of compound D, while the expression level of pparγ gradually decreased with increasing concentration of compound D. These results indicate that compound D is a FoxO1 agonist that significantly activates FoxO1 transcription levels.
5. SH-SY5Y cells were grown at 1.5X10 per well 4 After 24h incubation in 96-well plates, the culture broth containing different concentrations of compound D was added, and after 24h cellular proteins and supernatants were collected, using the humanβ -amyl (1-40) and β -amyl (1-42) ELISA kits, as shown in fig. 5, compound D was found to reduce aβ1-40 and aβ1-42 production.
6. To study the mechanism of action of compound D, levels of related proteins APP, ADAM10, PS1 and BACE1 in aβ metabolic processes were examined. As shown in fig. 6, the expression level of BACE1 was found to decrease significantly with increasing concentration of compound D. There was no significant difference in expression of APP, ADAM10 and PS1 under compound D treatment. In general, compound D down-regulates expression of BACE1 by SH-SY5Y cells at high concentrations, thereby significantly down-regulating levels of Aβ1-40, Aβ1-42 in SH-SY5Y cells and in culture supernatant, compound D has potential therapeutic effects on AD as a FoxO1 agonist.
Claims (1)
- Use of n- (3-methyl-5-isothiazolyl) -2-oxo-3- (2H) -benzoxazole acetamides for the manufacture of a medicament for the prevention and treatment of alzheimer's disease by lowering aβ1-40 or aβ1-42 and reducing BACE1, having the structural formula:。/>
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1708484A (en) * | 2002-11-08 | 2005-12-14 | 麦克公司 | Ophthalmic compositions for treating ocular hypertension |
| CN1989117A (en) * | 2004-07-22 | 2007-06-27 | 弗·哈夫曼-拉罗切有限公司 | Substituted benzothiazoles |
| WO2010139982A1 (en) * | 2009-06-02 | 2010-12-09 | The University Of Sheffield | Indole derivatives for the stimulation of stem cell proliferation |
| CN102639530A (en) * | 2009-11-27 | 2012-08-15 | 詹森药业有限公司 | Morpholinothiazoles as alpha 7 positive allosteric modulators |
| TW201720438A (en) * | 2015-08-26 | 2017-06-16 | 艾奇利恩製藥股份有限公司 | Compounds for the treatment of medical disorders |
| CN110656170A (en) * | 2019-11-08 | 2020-01-07 | 新乡医学院 | Reagent, diagnostic product and therapeutic composition for Alzheimer disease diagnosis, candidate drug screening method and application |
| CA3148903A1 (en) * | 2019-08-06 | 2021-02-11 | Shanghai Green Valley Pharmaceutical Co., Ltd. | Method for treating alzheimer's disease by inhibiting uptake of amino acids by t cells |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11649228B2 (en) * | 2018-10-29 | 2023-05-16 | The Board Of Regents Of The University Of Texas System | Zinc indicators for cellular imaging |
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1708484A (en) * | 2002-11-08 | 2005-12-14 | 麦克公司 | Ophthalmic compositions for treating ocular hypertension |
| CN1989117A (en) * | 2004-07-22 | 2007-06-27 | 弗·哈夫曼-拉罗切有限公司 | Substituted benzothiazoles |
| WO2010139982A1 (en) * | 2009-06-02 | 2010-12-09 | The University Of Sheffield | Indole derivatives for the stimulation of stem cell proliferation |
| CN102639530A (en) * | 2009-11-27 | 2012-08-15 | 詹森药业有限公司 | Morpholinothiazoles as alpha 7 positive allosteric modulators |
| TW201720438A (en) * | 2015-08-26 | 2017-06-16 | 艾奇利恩製藥股份有限公司 | Compounds for the treatment of medical disorders |
| CA3148903A1 (en) * | 2019-08-06 | 2021-02-11 | Shanghai Green Valley Pharmaceutical Co., Ltd. | Method for treating alzheimer's disease by inhibiting uptake of amino acids by t cells |
| CN110656170A (en) * | 2019-11-08 | 2020-01-07 | 新乡医学院 | Reagent, diagnostic product and therapeutic composition for Alzheimer disease diagnosis, candidate drug screening method and application |
Non-Patent Citations (4)
| Title |
|---|
| "补肾活血"针刺法对SAMP8小鼠海马蛋白质表达的影响;朱宏;董克礼;李广城;肖岚;;中国老年学杂志(第23期);第4613-4616页 * |
| FoxO1 overexpression reduces Aβ production and tau phosphorylation in vitro;Wei Zhang et al.，;《Neuroscience Letters》;第1-6页 * |
| In silico and in vitro analyses of a novel FoxO1 agonist reducing Aβ levels via downregulation of BACE1;Ming- Ti Lv et al.，;《CNS Neurosci Ther》;第1-11页 * |
| 阿尔茨海默病重要分泌酶BACEl及其抑制剂;张顼等;《神经疾病与精神卫生》;第9卷(第1期);第1-7页 * |
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