CN111205308B - Sulfo-diketone piperazine compound and preparation method and application thereof - Google Patents
Sulfo-diketone piperazine compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN111205308B CN111205308B CN202010057556.XA CN202010057556A CN111205308B CN 111205308 B CN111205308 B CN 111205308B CN 202010057556 A CN202010057556 A CN 202010057556A CN 111205308 B CN111205308 B CN 111205308B
- Authority
- CN
- China
- Prior art keywords
- compound
- thiodiketopiperazine
- methanol
- dichloromethane
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a microbial medicine technology, in particular to a preparation method and application of a thiodiketopiperazine compound, wherein the thiodiketopiperazine compound is derived from a fermentation product of epicoccum nigrum. The molecular formula of the compound is C19H22N2O7S2The structure is shown in formula I; the compound obtained by the invention has the same positive control sorafenib (IC)50Value of 8.2. mu.M) comparable activity against Huh7.5 hepatoma cells, IC50The value is 9.5 mu M, and the compound can be fermented and produced by microorganisms, and is expected to be further developed into an anti-liver cancer medicament or a lead compound thereof.
Description
Technical Field
The invention relates to the technical field of microbial medicines, in particular to a thiodione piperazine compound obtained from a fermentation product of epicoccum nigrum, and a preparation method and application thereof.
Background
Liver cancer is still one of the most serious diseases at present, and although researchers are working on finding better prevention and treatment schemes, the incidence and mortality of liver cancer still have a rapid trend in recent years, and the development of novel drugs for inhibiting the occurrence of tumor diseases is urgently needed.
The thiodione piperazine compounds are important components of sulfur-containing metabolites of fungi, are common metabolites of epicoccum nigrum, umbilicaria oris and the like, and have good biological activity. The invention relates to a novel thiodiketopiperazine compound containing an intra-disulfide bridge structure, which is obtained from epicoccum nigrum.
Disclosure of Invention
The invention aims to provide a thiodiketopiperazine compound obtained from a fermentation product of epicoccum nigrum, and a preparation method and application thereof.
In order to achieve the purpose, the invention adopts the technical scheme that:
a thiodiketopiperazine compound is shown as formula I, and the molecular formula is C19H22N2O7S2；
A preparation method of a thiodiketopiperazine compound comprises the following steps:
fermenting and culturing the activated epicoccum nigrum mycelium in a solid culture medium, and purifying to obtain the thiodione piperazine compound shown in the formula I; the formula of the solid culture medium is as follows: every 100 ml of seawater contains 70 g of rice, 0.2 g of corn steep liquor, 0.3 g of peptone, 0.5 g of yeast powder, 0.1 g of monosodium glutamate and Fe2(SO4)30.002 g, MgSO4·7H2O0.07 g, ZnSO40.0001 g, KH2PO40.025 g.
The method specifically comprises the following steps:
1) culturing Epicoccum nigrum on PDA (potato sucrose agar) culture medium at 28 deg.C for 7 days, inoculating its mycelium in solid culture medium, standing at room temperature for fermenting for 35 days, extracting the fermented product with petroleum ether to remove small polar product, soaking in ethyl acetate, repeatedly extracting, mixing extractive solutions, and concentrating to obtain crude extract;
2) subjecting the crude extract to reduced pressure silica gel column chromatography, sequentially subjecting to gradient elution with petroleum ether-ethyl acetate and dichloromethane-methanol elution systems with gradient of 20:1 to 1:1(v/v, the same applies below), collecting dichloromethane-methanol 20:1 eluate, subjecting to reduced pressure silica gel column chromatography again, and subjecting to gradient elution with dichloromethane-acetone elution systems with gradient of 50:1 to 1:1 again;
3) collecting the components eluted by 50:1 and 20:1 of dichloromethane-acetone in the step 2), combining, concentrating, performing reverse phase silica gel column chromatography, and performing gradient elution by using a methanol-water elution system with gradient of 10: 90-100: 0;
4) collecting the component of methanol-water 20:80 in the step 3), carrying out normal phase silica gel column chromatography, eluting with a dichloromethane-methanol system of 150:1 to 10:1, collecting the component of dichloromethane-methanol 100:1, purifying by Sephadex LH-20 methanol gel column chromatography, detecting by TLC, using dichloromethane-methanol 20:1 as a developing agent, wherein the Rf value is 0.4, and sulfuric acid-anisaldehyde develops a single uniform yellow point to obtain the thiodiketopiperazine compound shown in the formula I.
In a still further aspect of the present invention,
1) culturing epicoccum nigrum on a PDA (potato sucrose agar) culture medium at 28 ℃ for 7 days, inoculating well-grown epicoccum nigrum mycelia into a sterile solid culture medium, standing and fermenting at room temperature for 35 days, extracting a fermentation product by petroleum ether to remove a small-polarity product, fully soaking and extracting by ethyl acetate for 4 times, and mixing and concentrating to obtain a crude extract;
2) subjecting the crude extract to reduced pressure silica gel (100-200 mesh) column chromatography, performing gradient elution with petroleum ether-ethyl acetate 20:1, 10:1, 5:1, 2:1, 1:1(v/v, the same below) and dichloromethane-methanol 20:1, 10:1, 5:1, 1:1 elution systems in sequence, collecting dichloromethane-methanol 20:1 eluate, and subjecting the dichloromethane-methanol 20:1 eluate to reduced pressure silica gel column chromatography again, wherein the gradient of the elution system is 50:1, 20:1, 10:1, 5:1, 2:1, 1:1 dichloromethane-acetone;
3) collecting the dichloromethane-acetone 50:1 and 20:1 components in the step 2), mixing, performing reverse phase silica gel column chromatography, and eluting with methanol-water of 10: 90-100: 0;
4) collecting the components of the methanol-water 20:80 in the step 3), carrying out normal phase silica gel column chromatography, eluting with dichloromethane-methanol of 150:1 to 10:1, collecting the components of the dichloromethane-methanol of 100:1, purifying by Sephadex LH-20 methanol gel column chromatography, detecting by TLC, wherein a developing agent is dichloromethane-methanol 20:1, the Rf value is 0.4, and the sulfuric acid-anisaldehyde develops color to form a single uniform yellow point, thus obtaining the purified target compound.
An application of a thiodiketopiperazine compound, namely an application of the thiodiketopiperazine compound in the formula I as an anticancer drug or a lead compound.
The thiodiketopiperazine compound in the formula I is applied to being used as an anti-liver cancer drug or a lead compound.
The liver cancer is Huh7.5 liver cancer cells.
The invention has the advantages that:
1. the prepared thiodione piperazine compound is derived from a fermentation product of epicoccum nigrum, and the compound prepared by a microbial fermentation method has the characteristics of high efficiency and environmental protection;
2. the thiodiketopiperazine compound prepared by the invention has significant Huh7.5 hepatoma cell resisting activity, and is a novel compound which is not reported yet and IC of the compound50The value (9.5 mu M) is equivalent to that of the positive control sorafenib (8.2 mu M), and the action mechanism of the sorafenib can be further explored so as to be developed into a novel anti-liver cancer drug or a lead compound thereof.
Detailed Description
The invention will now be further illustrated with reference to some non-limiting specific examples.
Example 1 structural formula of the Compound
The structure of the thiodiketopiperazine compound separated from the epicoccum nigrum fermentation product is shown as the formula (I) (the Arabic numerals in the formula represent the carbon atom mark position in the chemical structure):
example 2 preparation of Compounds of formula I
1) Fermentation culture
Epicoccum nigrum (Epicoccum purpurascens Ehveub ex Schlecht, also known as Epicoccum nigrum, prunus, south royal, picloram, caokouqiang, anshi agriculture, 2010,38(6), 2988-containing 2990) is used for producing white mycelium on a PDA (potato sucrose agar) culture medium, generating brown spores at the later stage, culturing for 7 days at 28 ℃, inoculating the mycelium into a sterile solid culture medium, standing and culturing for 35 days at room temperature, extracting a fermentation product by petroleum ether to remove small-polarity products, soaking and extracting for 4 times by using ethyl acetate, combining and concentrating to obtain a fermentation crude extract;
the formula of the solid culture medium is as follows: every 100 ml of seawater contains 70 g of rice, 0.2 g of corn steep liquor, 0.3 g of peptone, 0.5 g of yeast powder, 0.1 g of monosodium glutamate and Fe2(SO4)30.002 g, MgSO4·7H2O0.07 g, ZnSO40.0001 g, KH2PO40.025 g;
2) separating and purifying crude extract
The crude extract is segmented by reduced pressure silica gel (100-200 meshes) column chromatography, and gradient elution is carried out by using petroleum ether-ethyl acetate with gradient of 20:1 to 1:1(20:1, 10:1, 5:1, 2:1, 1:1, v/v, the same applies below) and dichloromethane-methanol with gradient of 20:1 to 1:1(20:1, 10:1, 5:1, 1:1) as elution solvents in sequence; collecting the component eluted by dichloromethane-methanol 20:1, and performing reduced pressure silica gel column chromatography again, wherein the elution system is dichloromethane-acetone with the ratio of 50:1 to 1:1(50:1, 20:1, 10:1, 5:1, 2:1 and 1: 1);
collecting the dichloromethane-acetone 50:1 and 20:1 components, mixing, performing reverse phase silica gel column chromatography, and sequentially performing gradient elution with methanol-water at ratio of 10: 90-100: 0;
collecting the components of the methanol-water in a ratio of 20:80, carrying out normal phase silica gel column chromatography, eluting with dichloromethane-methanol in a ratio of 150:1 to 10:1, collecting the components of the dichloromethane-methanol in a ratio of 100:1, purifying by Sephadex LH-20 methanol gel column chromatography, detecting by TLC, wherein a developing agent is dichloromethane-methanol in a ratio of 20:1, the Rf value is 0.4, and sulfuric acid-anisaldehyde is developed into a single uniform yellow point to obtain a purified target compound. The structure of the compound is identified as the compound shown in the formula I,
the compound has the following physicochemical and spectral characteristics:
a white solid; specific rotation
-215.4 (c 0.13, MeOH); ultraviolet UV (MeOH) lambdamax(log ε)201(4.06) nm; circular dichroism CD (2.20mM, MeOH) lambdamax(Δ ε)200(+0.43),234 (-2.24), 265(+0.53) nm; hydrogen nuclear magnetic resonance spectrum (500MHz, solvent is deuterated dimethyl sulfoxide) deltaH：2.68(m，Hα-3)，2.99(dd，J＝14.8，8.3Hz，Hβ-3)，3.18(t，J＝7.4Hz，H-4)，2.71(m，Hα-6)，2.61(m，Hβ-6)，3.29(ddd，J＝10.9，4.8，1.5Hz，H-7)，5.03(t，J＝4.4Hz，H-8)，4.41(dd，J＝7.4，4.4Hz，H-9)，2.74(m，Hα-3')，2.93(dd，J＝14.8，8.2Hz，Hβ-3')，3.23(t，J＝7.6Hz，H-4')，2.66(m，Hα-6')，2.27(dt，J＝16.7，4.1Hz，Hβ-6')，1.62(td，J＝12.5，5.0Hz，Hα-7')，1.89(m，Hβ-7'), 4.81(q, J ═ 4.6Hz, H-8'), 4.36(ddd, J ═ 7.6, 3.7, 1.6Hz, H-9'), 5.64(d, J ═ 4.7Hz, OH-8), 5.49(d, J ═ 4.0Hz, OH-8'), 3.21(s, OMe-7); nuclear magnetic resonance carbon spectrum (125MHz, solvent is deuterated dimethyl sulfoxide) deltaC：162.2(C，C-1)，76.2(C，C-2)，32.6(CH2，C-3)46.4(CH，C-4)，207.8(C，C-5)，40.7(CH2，C-6)，75.5(CH，C-7)，61.9(CH，C-8)，63.2(CH，C-9)，162.2(C，C-1')，76.4(C，C-2')，32.2(CH2，C-3')，46.7(CH，C-4')，208.6(C，C-5')，33.9(CH2，C-6')，25.4(CH2，C-7')，60.8(CH，C-8')，65.8(CH，C-9')，56.0(CH3OMe-7); high resolution ESI mass spectrum [ M + H ]]+m/z 455.0930,C19H23O7N2S2Calculated value 455.0941). (nuclear magnetic signal attribution is based on DEPT, COSY, HSQC and HMBC atlas analysis results, the multiplicity of carbon signals is determined by DEPT method.)
Example 3 antitumor Activity test
1) Test cell line and culture thereof
The test cell strain adopted by the invention is a Huh7.5 hepatoma cell strain, and the Huh7.5 cells are cultured in an RPMI-1640 culture medium containing 10% fetal calf serum, 100U/ml penicillin and 100mg/ml streptomycin. All experiments were performed using the same cell line between passage 2 and passage 5.
2) Preparation of sample to be tested
The test sample was the pure compound obtained in the above example, and 1.8 mg of the compound was accurately weighed and dissolved in 200. mu.l of DMSO, and mixed well to prepare a sample solution to be tested having a concentration of 20 mM. Aspirate 100 microliters of sample solution into another centrifuge tube and add 100 microliters of DMSO to give a sample solution of halved concentration. By analogy, 5 sets of sample solutions (20, 10, 5, 2.5 and 1.25mM) were obtained with successively halved concentrations. The positive control sorafenib was prepared as above.
3) Tumor cell growth inhibition activity test (MTT method):
the growth inhibitory activity of the tumor cells is tested by adopting a tetrazolium salt staining method (MTT method) so as to evaluate the action effect of the compound.
The principle of the test method is as follows: the tetrazolium salt MTT is an acceptable H+A yellow dye of (2). Exogenous MTT is reduced to Formazan (Formazan) in mitochondria of living cells by succinate dehydrogenase and cytochrome C, a water-insoluble bluish-purple crystal that deposits in cells after crystallization, whereas it is absent in dead cells because of succinate dehydrogenaseFormazan crystals cannot be formed. Moreover, in a certain cell quantity range, the generation amount of the formazan crystals is in direct proportion to the number of living cells, dimethyl sulfoxide (DMSO) can dissolve the formazan deposited in the cells, and a maximum absorption peak is formed at a position of 570 nanometers, so that the number of the living cells can be indirectly reflected by detecting the light absorption value of the formazan at the position of 570 nanometers of wavelength by using an enzyme labeling instrument, and the influence of the drug on cell proliferation is evaluated.
The test flow comprises the following steps: taking Huh7.5 liver cancer cells in logarithmic growth phase, wherein the cell density is 6 multiplied by 103Cells/ml were seeded into 96-well cell culture plates and then placed in an incubator with 5% carbon dioxide and incubated at 37 ℃ until a cell monolayer was confluent at the bottom of the well. The samples were set up in 5 concentration gradients 20, 10, 5, 2.5 and 1.25mM, three replicates per concentration, the blank was added to 96 well plates in order with DMSO instead of the sample solution, placed further in an incubator with 5% carbon dioxide, incubated at 37 ℃ for 16-48 hours and observed under an inverted microscope. Thereafter, MTT solution was added to each well at a concentration of 5 mg/ml, and the incubation was continued for 4 hours. After termination of the culture, the culture medium in the wells was carefully aspirated. Then 150. mu.l DMSO was added to each well, and the resulting mixture was shaken on a shaker for 10 minutes at a low speed to dissolve the crystals sufficiently, and then the absorbance (OD value) at 490 nm of each well was measured by a microplate reader.
Inhibition (IR%) calculation: OD values were averaged over three wells, formula: the calculated value of IR% ((OD blank-OD sample)/OD blank × 100%) was the inhibition rate (IR%) of the sample on cell proliferation.
IC50The value: the inhibition (IR%) was 50% of the corresponding concentration of the sample solution.
The experimental results are as follows: compound IC obtained by the invention50The value was 9.5. mu.M, positive control sorafenib IC50The value was 8.2. mu.M.
The experimental results prove that the compound has a strong growth inhibition effect on tested Huh7.5 liver cancer cells, has an effect equivalent to that of sorafenib serving as a positive control, can be prepared into an anti-tumor medicament or a lead compound, and is expected to be applied to development of related medicaments in the form of any pharmaceutically acceptable salt or pharmaceutically acceptable auxiliary materials including carriers such as excipients, diluents and the like.
Claims (6)
1. A thiodiketopiperazine compound, characterized in that: the molecular formula of the thiodiketopiperazine compound is C19H22N2O7S2The structure of the compound is shown in a formula I:
formula I.
2. A process for the preparation of thiodiketopiperazine compounds according to claim 1, characterized in that: fermenting and culturing the activated epicoccum nigrum mycelium in a solid culture medium, and purifying to obtain the thiodione piperazine compound shown in the formula I; the formula of the solid culture medium is as follows: every 100 ml of seawater contains 70 g of rice, 0.2 g of corn steep liquor, 0.3 g of peptone, 0.5 g of yeast powder, 0.1 g of monosodium glutamate and Fe2(SO4)3 0.002 g, MgSO4·7H2O0.07 g, ZnSO4 0.0001 g, KH2PO4 0.025 g.
3. The process for the preparation of thiodiketopiperazine compounds according to claim 2, characterized in that:
1) culturing epicoccum nigrum on a PDA culture medium at 28 ℃ for 7 days, inoculating mycelium of the epicoccum nigrum in a solid culture medium, standing and fermenting at room temperature for 35 days, fully soaking and repeatedly extracting a fermentation product by using ethyl acetate after removing a small-polarity product by petroleum ether extraction, combining extract liquor and concentrating to obtain a crude extract;
2) performing reduced pressure silica gel column chromatography on the crude extract, sequentially performing gradient elution by using petroleum ether-ethyl acetate with the volume ratio of 20:1 to 1:1 and a dichloromethane-methanol elution system with the volume ratio of 20:1 to 1:1 respectively, collecting components obtained by dichloromethane-methanol elution with the volume ratio of 20:1, performing reduced pressure silica gel column chromatography again, and performing gradient elution again by using a dichloromethane-acetone elution system with the volume ratio of 50:1 to 1: 1;
3) collecting dichloromethane-acetone eluted components with volume ratios of 50:1 and 20:1 in the step 2), combining, concentrating, performing reverse phase silica gel column chromatography, and performing gradient elution by using a methanol-water elution system with a gradient of volume ratio of 10:90 to 100: 0;
4) collecting the component of methanol-water 20:80 in the step 3), carrying out normal phase silica gel column chromatography, eluting with a dichloromethane-methanol system with a volume ratio of 150:1 to 10:1, collecting the component of dichloromethane-methanol with a volume ratio of 100:1, purifying by Sephadex LH-20 methanol gel column chromatography, detecting by TLC, using a developing agent of dichloromethane-methanol with a volume ratio of 20:1, wherein the Rf value is 0.4, and the sulfuric acid-anisaldehyde develops color to form a single uniform yellow point, so as to obtain the thiodiketopiperazine compound shown in the formula I.
4. Use of a thiodiketopiperazine compound according to claim 1, characterized in that: the thiodiketopiperazine compound in the formula I is applied to preparation of anticancer drugs or lead compounds.
5. The use of thiodiketopiperazine compounds according to claim 4, characterized in that: the thiodiketopiperazine compound in the formula I is applied to preparation of anti-liver cancer drugs or lead compounds.
6. The use of thiodiketopiperazine compounds according to claim 5, characterized in that: the liver cancer is Huh7.5 liver cancer cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010057556.XA CN111205308B (en) | 2020-01-19 | 2020-01-19 | Sulfo-diketone piperazine compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010057556.XA CN111205308B (en) | 2020-01-19 | 2020-01-19 | Sulfo-diketone piperazine compound and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111205308A CN111205308A (en) | 2020-05-29 |
| CN111205308B true CN111205308B (en) | 2022-03-15 |
Family
ID=70785353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010057556.XA Active CN111205308B (en) | 2020-01-19 | 2020-01-19 | Sulfo-diketone piperazine compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111205308B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0262880A (en) * | 1988-08-29 | 1990-03-02 | Taisho Pharmaceut Co Ltd | Dithiodiketopiperazine compound |
| CN104031051A (en) * | 2014-05-20 | 2014-09-10 | 宁波大学 | Diketopiperazines and preparation method and application thereof |
| CN104804020A (en) * | 2014-01-29 | 2015-07-29 | 中国科学院海洋研究所 | Sulfodionepiperazine compound, and preparation method and use thereof |
| CN105229013A (en) * | 2013-05-24 | 2016-01-06 | 梨花女子大学校产学协力团 | Epidithio-dioxypiperazine piperazine compound or its derivative, and uses thereof |
| JP2019070010A (en) * | 2012-10-22 | 2019-05-09 | シティ・オブ・ホープＣｉｔｙ ｏｆ Ｈｏｐｅ | ETP derivative |
-
2020
- 2020-01-19 CN CN202010057556.XA patent/CN111205308B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0262880A (en) * | 1988-08-29 | 1990-03-02 | Taisho Pharmaceut Co Ltd | Dithiodiketopiperazine compound |
| JP2019070010A (en) * | 2012-10-22 | 2019-05-09 | シティ・オブ・ホープＣｉｔｙ ｏｆ Ｈｏｐｅ | ETP derivative |
| CN105229013A (en) * | 2013-05-24 | 2016-01-06 | 梨花女子大学校产学协力团 | Epidithio-dioxypiperazine piperazine compound or its derivative, and uses thereof |
| CN104804020A (en) * | 2014-01-29 | 2015-07-29 | 中国科学院海洋研究所 | Sulfodionepiperazine compound, and preparation method and use thereof |
| CN104031051A (en) * | 2014-05-20 | 2014-09-10 | 宁波大学 | Diketopiperazines and preparation method and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| Brocazines A-F, Cytotoxic Bisthiodiketopiperazine Derivatives from Penicillium brocae MA-231, an Endophytic Fungus Derived from the Marine Mangrove Plant Avicennia marina;Ling-Hong Meng et al.,;《J. Nat. Prod.》;20140808;第77卷;第1921-1927页 * |
| Cytotoxic Thiodiketopiperazine Derivatives from the Deep Sea-Derived Fungus Epicoccum nigrum SD-388;Lu-Ping Chi et al.;《Mar. Drugs》;20200313;第18卷;第1-12页 * |
| Isolation and Structure Assignments of Rostratins A-D, Cytotoxic Disulfides Produced by the Marine-Derived Fungus Exserohilum rostratum;Ren Xiang Tan et al.;《J. Nat. Prod.》;20040710;第67卷(第8期);第1374-1382页 * |
| Thiodiketopiperazines Produced by the Endophytic Fungus Epicoccum nigrum;Jia-Ming Wang et al.,;《J. Nat. Prod.》;20100615;第73卷;第1240-1249页 * |
| 多硫代二酮哌嗪类化合物的研究进展;李莉媛 等;《中国抗生素杂志》;20130331;第38卷(第3期);第161-174页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111205308A (en) | 2020-05-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108299462B (en) | Mixed source terpene compound and separation method and application thereof | |
| CN107298672B (en) | Application of seclenic acid I derived from penicillium oxalicum in preparation of anti-human colon cancer drugs | |
| CN110407847B (en) | Azaphilones compounds obtained from aspergillus terreus and preparation and application thereof | |
| CN109134574B (en) | Steroid compound, preparation method and application thereof, and anti-tumor drug | |
| CN113603744A (en) | Betulonic acid derivative and preparation method thereof | |
| CN109942658B (en) | Heteroterpene compounds, preparation method and application thereof, and antitumor drugs | |
| CN109985044B (en) | Application of betulin and its derivatives in preparing antitumor drugs | |
| CN111205308B (en) | Sulfo-diketone piperazine compound and preparation method and application thereof | |
| CN114213428B (en) | Indole alkaloid compound and preparation method and application thereof | |
| CN116120222A (en) | Antitumor and antiviral compound Talachalasin A-C and preparation method and application thereof | |
| CN113861208B (en) | Cytochalasin compound and preparation method and application thereof | |
| CN114085272B (en) | Isaridin cyclic depsipeptide derivative and preparation method and application thereof | |
| CN113603594B (en) | Sesquiterpenoids, preparation method thereof and application thereof in preparing antitumor drugs | |
| CN109134416B (en) | Application of seclenic acid H derived from penicillium oxalicum in preparation of human cervical cancer drugs | |
| CN115252624A (en) | Betulinic acid derivative and preparation method and application thereof | |
| CN112500348B (en) | Geldanamycin derivatives, preparation method thereof and application thereof in preparing antitumor drugs | |
| CN115403556A (en) | Pentanone thiophene compounds, preparation method thereof and application thereof in anti-inflammatory drugs | |
| CN111808088B (en) | Compounds tersaphilone B and E, preparation method thereof and application thereof in preparing antitumor drugs | |
| CN111808015B (en) | Phenylalanine-derived cytochalasin as well as preparation method and application thereof | |
| CN111235042A (en) | Butenolide dimer with COX-2 inhibition and antioxidation effects and application thereof | |
| CN114891017B (en) | Maleic anhydride alicyclic compound and preparation method and application thereof | |
| CN114605430B (en) | Macrocyclic dilactone compound, and preparation method and application thereof | |
| CN104059038A (en) | Sesquiterpene compounds and application thereof | |
| CN114230578B (en) | Diketomorpholine alkaloid compound and preparation method and application thereof | |
| CN111995560B (en) | Monoterpene indole compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |