CN115154460A - Application of macrocyclic compound in preparation of medicine for treating hemangioma - Google Patents
Application of macrocyclic compound in preparation of medicine for treating hemangioma Download PDFInfo
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- CN115154460A CN115154460A CN202210954722.5A CN202210954722A CN115154460A CN 115154460 A CN115154460 A CN 115154460A CN 202210954722 A CN202210954722 A CN 202210954722A CN 115154460 A CN115154460 A CN 115154460A
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- Prior art keywords
- zearalenone
- compound
- hemangioma
- application
- macrocyclic compound
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- 201000011066 hemangioma Diseases 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 150000002678 macrocyclic compounds Chemical class 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 5
- MBMQEIFVQACCCH-UHFFFAOYSA-N trans-Zearalenon Natural products O=C1OC(C)CCCC(=O)CCCC=CC2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-UHFFFAOYSA-N 0.000 claims abstract description 30
- MBMQEIFVQACCCH-QBODLPLBSA-N zearalenone Chemical compound O=C1O[C@@H](C)CCCC(=O)CCC\C=C\C2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-QBODLPLBSA-N 0.000 claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 230000006907 apoptotic process Effects 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 4
- -1 beta-resorcinolic acid lactone Chemical class 0.000 claims abstract 2
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 230000002489 hematologic effect Effects 0.000 claims 2
- 230000009826 neoplastic cell growth Effects 0.000 claims 2
- 229940114055 beta-resorcylic acid Drugs 0.000 claims 1
- UIAFKZKHHVMJGS-UHFFFAOYSA-N beta-resorcylic acid Natural products OC(=O)C1=CC=C(O)C=C1O UIAFKZKHHVMJGS-UHFFFAOYSA-N 0.000 claims 1
- 239000002075 main ingredient Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 abstract description 6
- 230000022534 cell killing Effects 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 2
- 230000022131 cell cycle Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 28
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- 201000005787 hematologic cancer Diseases 0.000 description 4
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 3
- 241001024304 Mino Species 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 206010067572 Oestrogenic effect Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229960001755 resorcinol Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Images
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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Abstract
The invention provides an application of a macrocyclic compound in preparing a medicine for treating hemangioma, wherein the macrocyclic compound is zearalenone with a chemical name of: 6- (10-hydroxy-6-oxy-undecenyl) beta-resorcinolic acid lactone. The experiment of the invention proves that the compound zearalenone can generate obvious cell killing effect on the blood tumor continuous cell line and simultaneously obviously induce the blood tumor continuous cell line to generate cell apoptosis and cycle retardation. The invention provides a brand-new treatment means for clinical treatment of hemangioma, and widens the application field of the compound zearalenone.
Description
Technical Field
The invention belongs to the field of application of compounds, and relates to application of a macrocyclic compound in preparation of a medicine for treating hemangioma, wherein the macrocyclic compound is zearalenone.
Background
Hematological tumors mainly include various leukemias, multiple myeloma, and malignant lymphoma, which are located in front of global tumor morbidity and mortality. Moreover, the hematological tumor has the characteristics of high malignancy, complex treatment, poorer prognosis and the like, and is a serious disease which seriously harms human health. At present, the clinical treatment of the hematological tumor is mainly combined therapy mainly comprising chemotherapy, but the clinical response rate is poor, and the drug resistance and disease recurrence of a patient can be caused. Stem cell transplantation therapy is expensive and has certain complications. Although there are some targeted therapies and immunotherapy methods, the drug alternatives for hematologic tumors are still rare and have poor therapeutic effect, so that the development of new drugs for clinical treatment of hematologic tumors is still needed to improve the survival and prognosis of patients with hematologic tumors.
The macrocyclic compound zearalenone, originally isolated from maize with head blight, has been shown to have estrogenic effects, acting primarily on the reproductive system, resulting in increased estrogen levels in poultry and livestock. Zearalenone is reported to produce cytotoxicity via Reactive Oxygen Species (ROS), thereby causing apoptosis of uterine cells. However, reports have not been found to show that zearalenone can inhibit the proliferation of blood tumor cells, induce apoptosis and cycle block of the blood tumor cells, and further improve the clinical medication problem of the blood tumor cells.
Disclosure of Invention
The invention aims to provide an application of a macrocyclic compound in preparing a medicament for treating hemangioma, wherein the macrocyclic compound is zearalenone with a chemical name of 6- (10-hydroxy-6-oxy-undecylenyl) beta-resorcin and a molecular formula of C 18 H 22 O 5 . The medicine is prepared by taking zearalenone and pharmaceutically acceptable salts thereof as one of main components and adding pharmaceutically acceptable auxiliary materials.
Furthermore, in vitro experiments prove that the zearalenone plays a role in treating the hemangioma by inducing the hemangioma continuous cell line MV4-11 to undergo apoptosis and cycle arrest, and the effective action concentration range of the zearalenone is 0.8-20 mu M.
The invention provides a brand new treatment means for clinical treatment of the hemangioma. The in vitro experiment proves that the zearalenone can generate obvious cell killing effect on the hemangioma-derived cell line, and simultaneously proves that the compound can induce the hemangioma-derived cell line to generate apoptosis and cycle arrest. The invention widens the application field of the compound zearalenone, provides a thought for the research and development of hematological tumor medicaments, and provides possibility for further improving the survival and prognosis conditions of hematological tumor patients (especially acute myeloid leukemia and lymphoma).
Drawings
FIG. 1 is a graph showing the effect of zearalenone at various concentrations on the cell viability of the continuous cell line MV4-11 of acute myeloid leukemia.
FIG. 2 is a graph of the effect of varying concentrations of the compound zearalenone on cell viability of the lymphoma continuous cell line Mino.
FIG. 3 is a graph showing the measurement of the apoptosis-inducing ability of zearalenone, a compound, to the acute myelogenous leukemia continuous cell line MV4-11, at various concentrations.
FIG. 4 shows the effect of zearalenone at various concentrations to induce cycle arrest in the acute myeloid leukemia continuous cell line MV 4-11.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings and examples. The following examples are intended to illustrate the invention only and are not intended to limit the scope of the invention.
The experimental procedures for which specific conditions are not specified in the examples are generally carried out according to conventional conditions, for example as described in Sambrook et al, molecular cloning: A Laboratory Manual (New York: cold Spring Harbor Laboratory Press, 1989), or according to the conditions recommended by the manufacturer.
The application of the compound zearalenone of the invention can refer to the conventional drug preparation method and actual development.
Example 1
MV4-11 cells and Mino cells were seeded in a 96-well plate at a density of 3000 cells per well, and the cells were treated with different concentrations of the compound zearalenone (20. Mu.M, 10. Mu.M, 5. Mu.M, 2.5. Mu.M, 1.25. Mu.M, 0.625. Mu.M, 0.3125. Mu.M, 0. Mu.M), respectively, 3 multiple wells were provided for each concentration group, and the survival of the cells was examined by the CCK-8 method 72 hours after the compound zearalenone had been allowed to act. The results show that the compound zearalenone with the concentration range of 2-20 mu M has obvious cell killing effect on two hemangioma cell strains. Half inhibitory concentrations (IC 50) of the compound zearalenone on MV4-11 and Mino cell lines were 3.063. Mu.M and 6.622. Mu.M, respectively. The results are shown in FIGS. 1 and 2.
Example 2
MV4-11 cells were seeded in a 24-well plate at a density of 20 ten thousand cells per well, MV4-11 cell lines were treated with different concentrations of the compound zearalenone (20. Mu.M, 10. Mu.M, 4. Mu.M, 0.8. Mu.M, 0.16. Mu.M, 0. Mu.M), respectively, and the proportion of apoptotic cells was determined by collecting cells 24 hours after the treatment. The cell suspension was resuspended in PBS and JC-1 staining solution was added, and then the cells were vortexed gently and incubated at 37 ℃ for 15 minutes in the absence of light. And (3) adding a staining buffer solution to wash the cells for 2 times, and detecting by using a flow cytometer after the reaction is finished. The results show that the compound zearalenone can induce significant apoptosis of MV4-11 cells in the concentration range of 0.8-20 μ M and is dose-dependent. The results are shown in FIG. 2.
Example 3
MV4-11 cells were seeded in 24-well plates at a density of 20 ten thousand cells per well, and MV4-11 cell lines were treated with different concentrations of the compound zearalenone (20. Mu.M, 10. Mu.M, 4. Mu.M, 0.8. Mu.M, 0.16. Mu.M, 0. Mu.M), respectively. After 24 hours of treatment, the cells were harvested, fixed in pre-cooled 70% ethanol at 4 ℃ for 24 hours, washed 2 times with PBS and treated with RNase. Performing flow measurement on the machine after PI dyeing. The results show that the compound zearalenone can induce significant cycle arrest of MV4-11 cells in the concentration range of 0.8-20 μ M, and is dose-dependent. The results are shown in FIG. 3.
Claims (3)
1. The application of a macrocyclic compound in the preparation of a medicament for treating hemangioma is characterized in that the compound is zearalenone with a chemical name of 6- (10-hydroxy-6-oxy-undecylenyl) beta-resorcylic acid lactone and a molecular formula of C 18 H 22 O 5 The chemical formula is:
2. the use of claim 1, wherein the zearalenone is effective for treating hematological neoplasia by inducing apoptosis and cycle arrest of the hematological neoplasia continuous cell line MV4-11, said zearalenone being effective at a concentration in the range of 0.8 μ M to 20 μ M.
3. The use of claim 1, wherein the medicament is prepared from zearalenone and pharmaceutically acceptable salts thereof as one of the main ingredients, with pharmaceutically acceptable excipients.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210954722.5A CN115154460A (en) | 2022-08-10 | 2022-08-10 | Application of macrocyclic compound in preparation of medicine for treating hemangioma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210954722.5A CN115154460A (en) | 2022-08-10 | 2022-08-10 | Application of macrocyclic compound in preparation of medicine for treating hemangioma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115154460A true CN115154460A (en) | 2022-10-11 |
Family
ID=83479974
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210954722.5A Pending CN115154460A (en) | 2022-08-10 | 2022-08-10 | Application of macrocyclic compound in preparation of medicine for treating hemangioma |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115154460A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1653059A (en) * | 2002-03-08 | 2005-08-10 | 卫材株式会社 | Macrocyclic compounds useful as pharmaceuticals |
| US20060079494A1 (en) * | 2004-09-27 | 2006-04-13 | Santi Daniel V | Specific kinase inhibitors |
| US20090048333A1 (en) * | 2007-07-25 | 2009-02-19 | Eisai Co., Ltd. | Zearalenone Macrolide Derivatives and Uses of the Same |
| US20090170925A1 (en) * | 2007-10-29 | 2009-07-02 | Eisai R&D Management Co., Ltd. | Methods for prognosing the ability of a zearalenone analog compound to treat cancer |
| US20140335050A1 (en) * | 2011-05-27 | 2014-11-13 | The General Hospital Corporation | Methods, compositions, and kits for the treatment of cancer |
-
2022
- 2022-08-10 CN CN202210954722.5A patent/CN115154460A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1653059A (en) * | 2002-03-08 | 2005-08-10 | 卫材株式会社 | Macrocyclic compounds useful as pharmaceuticals |
| US20060079494A1 (en) * | 2004-09-27 | 2006-04-13 | Santi Daniel V | Specific kinase inhibitors |
| US20090048333A1 (en) * | 2007-07-25 | 2009-02-19 | Eisai Co., Ltd. | Zearalenone Macrolide Derivatives and Uses of the Same |
| US20090170925A1 (en) * | 2007-10-29 | 2009-07-02 | Eisai R&D Management Co., Ltd. | Methods for prognosing the ability of a zearalenone analog compound to treat cancer |
| US20140335050A1 (en) * | 2011-05-27 | 2014-11-13 | The General Hospital Corporation | Methods, compositions, and kits for the treatment of cancer |
Non-Patent Citations (3)
| Title |
|---|
| BANJERDPONGCHAI, R.等: "Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells", 《JOURNAL OF HEMATOLOGY & ONCOLOGY》 * |
| 侯毅鞠等: "镰刀菌T-2毒素对人急性早幼粒白血病细胞HL60增殖与凋亡的影响", 《卫生研究》 * |
| 史嘉瑜等: "玉米赤霉烯酮中毒大鼠卵巢组织Caspase-3和Caspase-8的表达", 《中国兽医学报》 * |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20221011 |
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