CN103694209A - Marine fungus-derived acetophenone compounds and preparation method and application thereof - Google Patents
Marine fungus-derived acetophenone compounds and preparation method and application thereof Download PDFInfo
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- CN103694209A CN103694209A CN201310225664.3A CN201310225664A CN103694209A CN 103694209 A CN103694209 A CN 103694209A CN 201310225664 A CN201310225664 A CN 201310225664A CN 103694209 A CN103694209 A CN 103694209A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/38—Quinones containing —CHO or non—quinoid keto groups
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- 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
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
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- 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
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/66—Preparation of oxygen-containing organic compounds containing the quinoid structure
Abstract
The invention belongs to the technical field of medicament compounds, and particularly discloses marine fungus-derived acetophenone compounds, a preparation method and an application thereof. The acetophenone compounds have a structure of formula (I). The compounds 1 and 2 can significantly inhibit the activity of mycobacterium tuberculosis tyrosine phosphatase (mPTPB), and have IC50 values of 0.16+/-0.02 [mu]M and 1.37+/-0.03 [mu]M respectively; therefore, the compounds are applicable to preparation of novel anti-tuberculosis medicaments, and have wide application prospects.
Description
Technical field
The invention belongs to medical compounds technical field, specifically disclose the acetophenone compounds and preparation method thereof and application in a class thalassiomycetes source.
Background technology
Thalassiomycetes wide material sources, drug screening pick-up rate is high, compares with other marine organisms, and maximum advantage is exactly environmentally friendly, has the feature of sustainable development.Thalassiomycetes, among particular surroundings, has developed unique metabolic way, can produce novel structure, the significant all kinds of secondary metabolites of physiologically active.The multiple pharmaceutical uses such as that its meta-bolites has is antibacterial, antitumor, immunomodulatory, enzyme inhibition.At present, from comprise the marine microorganism of thalassiomycetes, find the focus that new medicine source has become international and domestic research.
Tuberculosis is the communicable disease of the serious harm human health that caused by mycobacterium tuberculosis (Mycobacterium tuberculosis).Development to the research of tuberculosis mechanism and the antituberculosis drug that carries out for special target spot is directly connected to the mankind's health and social development.Tyrosine phosphatase (mPTPB) by mycobacterium tuberculosis secretory is the important virulence factor of mycobacterium tuberculosis, is to cause phthisical major reason.MPTPB enters in scavenger cell after by mycobacterium tuberculosis secretory, stops the startup of host immune system, regulates the survival of bacillus in host.MPTPB is the new target spot of tuberculosis drug screening.The mPTPB that suppresses tubercule bacillus secretion, can stop tubercule bacillus to produce restraining effect to host immune, contributes to host to produce immunity to tubercule bacillus, thereby reaches treatment object lungy.
Summary of the invention
The object of the invention is in order to overcome the defect of anti-tuberculosis drugs inadequate resource in prior art, the acetophenone compounds in the thalassiomycetes source that a class is new is provided.Described acetophenone compounds is from a kind of thalassiomycetes mould
penicilliumwhat sp. in HN4-3A bacterial strain, separation obtained, this compound is inhibited to mycobacterium tuberculosis tyrosine phosphatase (mPTPB), can be applicable to prepare antituberculotic medicine.
Another object of the present invention is to provide the preparation method of above-mentioned new acetophenone compounds.
A further object of the present invention is to provide the application of above-mentioned acetophenone compounds in preparing anti-tuberculosis drugs.
Above-mentioned purpose of the present invention is achieved by the following technical programs:
One class acetophenone compounds, structural formula is as shown in formula I:
The preparation method of one class acetophenone compounds, comprises the steps:
S1. by thalassiomycetes mould
penicilliumsp. HN4-3A bacterial strain accesses seed culture medium, and shaking table is cultivated, and obtains seed culture fluid;
S2. seed culture fluid is accessed in fermention medium to standing cultivation;
S3. step S2 fermentation after product is filtered and obtains thalline and fermented liquid, fermented liquid, through ethyl acetate extraction, concentrating under reduced pressure, obtains medicinal extract, then through chromatographic separation, obtains acetophenone compounds shown in formula I 1 and 2;
Thalassiomycetes mould
penicilliumsp. HN4-3A bacterial strain is that separation obtains from the stem of Chinese Haikou, Hainan Province marine site mangrove acanthus Acanthus ilicifolius.Described thalassiomycetes mould
penicilliumsp. the depositary institution of HN4-3A bacterial strain is Chinese Typical Representative culture collection center, and preservation address is Wuhan, China city Wuhan University, and preserving number is CCTCC M 2013233, and preservation date is on May 27th, 2013.
As a kind of preferred version, in above-mentioned preparation method, the component of seed culture medium is described in step S1: glucose 35 ~ 40g, peptone 4 ~ 5g, yeast extract paste 4 ~ 5g, sea salt 4 ~ 5g, water 2L.Described in step S1, shaking table cultivation is at 26 ~ 28 ℃, shaking speed 150 ~ 200rpm, and incubation time is 60 ~ 72h.
As a kind of preferred version, in above-mentioned preparation method, the component of fermention medium is described in step S2: glucose 2000 ~ 2200g, peptone 180 ~ 200g, yeast extract paste 180 ~ 200g, sea salt 200 ~ 250g, water 100L.Described in step S2, the time of standing cultivation is 40 ~ 50 days, and the temperature of standing cultivation is 25 ~ 28 ℃.
As a kind of preferred version, in above-mentioned preparation method, fermented liquid is the ethyl acetate extraction that is 1: 1 by volume ratio described in step S3; Described medicinal extract carries out separation with silica gel column chromatography, uses respectively ethyl acetate-sherwood oil gradient elution of 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 100%.Described 30% ethyl acetate-sherwood oil wash-out partly passes through dextrane gel Sephadex LH-20 chromatography, and the methyl alcohol-chloroform that is 1:1 by volume ratio is that eluent carries out wash-out, and elutriant obtains compound shown in formula I 1 and 2 through recrystallization repeatedly.
The acetophenone compounds 1 that separation of the present invention obtains and 2 pairs of tubercule bacillus tyrosine phosphatases (mPTPB) have restraining effect significantly, therefore, can be used for preparing tubercule bacillus tyrosine phosphatase inhibitors.
Because tyrosine phosphatase (mPTPB) is the important virulence factor of mycobacterium tuberculosis, be to cause phthisical major reason, so the acetophenone compounds 1 and 2 that separation of the present invention obtains can be used for preparing anti-tuberculosis drugs.
Compared with prior art, the present invention has following beneficial effect:
Acetophenone compounds 1 and 2 of the present invention derives from thalassiomycetes, extracts separated method simple, with low cost from fungi; Acetophenone compounds 1 and 2 pairs of tubercule bacillus tyrosine phosphatases (mPTPB) have remarkable inhibiting activity, have a extensive future.
Embodiment
Below in conjunction with specific embodiment, further illustrate the present invention.The test method of using in embodiment if no special instructions, is ordinary method; The material using, reagent etc. if no special instructions, are reagent and the material that can obtain from commercial channels.
Embodiment 1
Acetophenone compounds 1 of the present invention and 2 can be from thalassiomycetes mould
penicilliumsp. in the fermented liquid of HN4-3A bacterial strain, separation obtains.Thalassiomycetes mould
penicilliumsp. HN4-3A is that separation obtains from the stem of marine site, Haikou mangrove acanthus Acanthus ilicifolius.Thalassiomycetes mould
penicilliumsp. HN4-3A bacterial strain is preserved in Chinese Typical Representative culture collection center on May 27th, 2013, and preservation address is Wuhan, China city Wuhan University, and preserving number is CCTCC M 2013233.
Concrete steps are as follows:
S1. seed culture:
S11. prepare seed culture medium: glucose 40g, peptone 4g, yeast extract paste 4g, sea salt 5g, tap water 2000mL, average mark is loaded on 8 500mL Erlenmeyer flasks, and 121 ℃ go out 25 minutes.
S12. the cultivation of seed: by thalassiomycetes mould
penicilliumsp. the bacterial strain of HN4-3A access seed culture medium, at the temperature of 28 ℃, puts on shaking table with the rotating speed of 200rpm, and cultivating 72 hours must seed culture fluid.
S2. fermentation culture:
S21. prepare fermention medium: glucose 2200g, peptone 200g, yeast extract paste 200g, sea salt 250g, tap water 100L, 121 ℃ go out 25 minutes.
S22. fermentation culture: the seed culture fluid access under aseptic technique, 5mL step S1 being obtained was equipped with in the Erlenmeyer flask of fermention medium, in 25 ℃ of standing cultivations 30 days.
S3. extract separated: the fermented product that step S2 fermentation is obtained filters to obtain thalline and fermented liquid, and the ethyl acetate that fermented liquid is 1:1 with volume ratio extracts, acetic acid ethyl acetate extract concentrating under reduced pressure at lower than 50 ℃ obtains medicinal extract 18.5g.This medicinal extract carries out separation through silica gel column chromatography, uses respectively 5%, 10%, 20%, 30%, 40%, 50%, 60%, ethyl acetate-sherwood oil gradient elution of 70%, 100%, wherein 30% ethyl acetate-sherwood oil wash-out part is through Sephadex LH-20 gel column, methyl alcohol-the chloroform that is 1:1 by volume ratio is eluent, repeatedly after chromatography and recrystallization, obtains this compound 1(15 mg) and 2(12 mg).
Embodiment 2
The separated compound 1 and 2 obtaining in embodiment 1 is carried out to structural analysis test, obtains following physico-chemical property data:
Compound 1: light yellow crystal, fusing point 286 ~ 287oC(thermometer is not proofreaied and correct), EI-MS (m/z): 398 [M]
+; HR-EI-MS(m/z): 398.1005[M]
+(theoretical value 398.1002).
Compound 2: light yellow crystal, fusing point 203 ~ 205oC(thermometer is not proofreaied and correct), EI-MS (m/z): 330 [M]
+, HR-EI-MS(m/z): 330.1101[M]
+(theoretical value 330.1103).
Compound 1 and 2 NMR data are in Table 1.
Table 1 compound 1 and 2 NMR data (125MHz/400MHz, TMS, ppm)
Through above data analysis, obtain the structural formula of compound 1 and compound 2, the structural formula of compound 1 and compound 2 is as shown in formula I:
Embodiment 3
Compound 1 in embodiment 1 and 2 is carried out to mycobacterium tuberculosis tyrosine phosphatase (mPTPB) and suppresses experiment:
Employing p-nitrophenyl phosphoric acid (
pnPP) be substrate, at 3 of 50mM, in 3-dimethylated pentanedioic acid damping fluid (25 ℃, pH 7.0), carry out.
pnPP is p-NP by mPTPB enzymolysis, measures the variation of its absorbancy and calculate the activity of enzyme with ultraviolet-visible spectrophotometer at 405nm wavelength place.React initial system 200 μ L, wherein comprise 5 enzymes of μ L, the substrate of 2.5mM
pthe inhibitor of NPP, different concns.Reaction starts after 5min, and the NaOH(concentration that adds immediately 50 μ L is 5mol/L) termination reaction, then, in transferase 12 00 μ L to 96 orifice plate, measure the light absorption value at 405nm wavelength place.
With following formula, calculate enzymic activity: inhibiting rate (%)=[(A
0– A)/A
0] * 100%, wherein A
0the absorbancy changing value of blank, the absorbancy changing value that A is sample.Measure the sample of 5 concentration, draw dosage-inhibiting rate curve, draw its IC
50value.Each sample replication three times, result represents with mean value ± standard deviation.
Result records compound
1with
2inhibited to mycobacterium tuberculosis tyrosine phosphatase (mPTPB), its IC
50be respectively 0.16 ± 0.02 μ M and 1.37 ± 0.03 μ M.
Claims (10)
1. a class acetophenone compounds, is characterized in that, structural formula is as shown in formula I:
2. the preparation method of acetophenone compounds described in claim 1, is characterized in that, comprises the steps:
S1. by thalassiomycetes mould
penicilliumsp. HN4-3A bacterial strain accesses seed culture medium, and shaking table is cultivated, and obtains seed culture fluid;
S2. seed culture fluid is accessed in fermention medium to standing cultivation;
S3. step S2 fermentation after product is filtered and obtains thalline and fermented liquid, fermented liquid, through ethyl acetate extraction, concentrating under reduced pressure, obtains medicinal extract, then through chromatographic separation, obtains compound shown in formula I 1 and 2;
Thalassiomycetes mould
penicilliumsp. HN4-3A bacterial strain is preserved in Chinese Typical Representative culture collection center on May 27th, 2013, and preserving number is CCTCC NO:M 2013233.
3. the preparation method of acetophenone compounds according to claim 2, is characterized in that, the component of seed culture medium is described in step S1: glucose 35 ~ 40g, peptone 4 ~ 5g, yeast extract paste 4 ~ 5g, sea salt 4 ~ 5g, water 2L.
4. the preparation method of acetophenone compounds according to claim 2, is characterized in that, to cultivate be at 26 ~ 28 ℃ to shaking table described in step S1, shaking speed 150 ~ 200rpm, and incubation time is 60 ~ 72h.
5. the preparation method of acetophenone compounds according to claim 2, is characterized in that the component of fermention medium is described in step S2: glucose 2000 ~ 2200g, peptone 180 ~ 200g, yeast extract paste 180 ~ 200g, sea salt 200 ~ 250g, water 100L.
6. the preparation method of acetophenone compounds according to claim 2, is characterized in that described in step S2 that the time of standing cultivation is 40 ~ 50 days, and the temperature of standing cultivation is 25 ~ 28 ℃.
7. the preparation method of acetophenone compounds according to claim 2, is characterized in that, fermented liquid is the ethyl acetate extraction that is 1: 1 by volume ratio described in step S3; Described medicinal extract carries out separation with silica gel column chromatography, uses respectively ethyl acetate-sherwood oil gradient elution of 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 100%.
8. the preparation method of acetophenone compounds according to claim 7, it is characterized in that, described 30% ethyl acetate-sherwood oil wash-out partly passes through dextrane gel Sephadex LH-20 chromatography, methyl alcohol-the chloroform that is 1:1 by volume ratio is that eluent carries out wash-out, and elutriant obtains compound shown in formula I 1 and 2 through recrystallization repeatedly.
9. the application of acetophenone compounds in preparing mycobacterium tuberculosis tyrosine phosphatase inhibitors described in claim 1.
10. the application of acetophenone compounds in preparing anti-tuberculosis drugs described in claim 1.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104311526A (en) * | 2014-09-13 | 2015-01-28 | 中山大学 | Marine fungus-derived dinaphthalene derivatives and their preparation method and use in tuberculosis resistance |
| CN104311525A (en) * | 2014-09-13 | 2015-01-28 | 中山大学 | Use of marine fungus-derived Azaphilone compound in preparation of antituberculosis drugs |
| CN107721972A (en) * | 2017-08-25 | 2018-02-23 | 中山大学 | The benzophenone analog derivative in a kind of marine fungi source and preparation method thereof and the application in antituberculotic is prepared |
| CN108441526A (en) * | 2017-02-04 | 2018-08-24 | 扬州大学 | A method of mass producing penicilone class compounds using marine fungi |
| CN109836395A (en) * | 2017-11-29 | 2019-06-04 | 扬州蓝色生物医药科技有限公司 | A kind of o-trifluoromethyl phenoxy acetamide base thiazole sulfonamide MptpB inhibitor |
| CN109836396A (en) * | 2017-11-29 | 2019-06-04 | 扬州蓝色生物医药科技有限公司 | A kind of novel thiazole sulfamide compound and its application as antituberculotic |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548439A (en) * | 2003-05-09 | 2004-11-24 | 中国医学科学院药物研究所 | Prepn of racemized and optically active poon essence A and its analog |
| WO2009059452A1 (en) * | 2007-11-05 | 2009-05-14 | Institute Of Mataria Medica, Chinese Academy Of Medical Sciences | Tetriacyclodipyranyl coumarins and the anti-hiv and anti-tuberculosis uses thereof |
| CN102732474A (en) * | 2012-05-21 | 2012-10-17 | 中山大学 | Compound for inhibiting mycobacterium tuberculosis, screening method and uses thereof |
-
2013
- 2013-06-07 CN CN201310225664.3A patent/CN103694209B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548439A (en) * | 2003-05-09 | 2004-11-24 | 中国医学科学院药物研究所 | Prepn of racemized and optically active poon essence A and its analog |
| WO2009059452A1 (en) * | 2007-11-05 | 2009-05-14 | Institute Of Mataria Medica, Chinese Academy Of Medical Sciences | Tetriacyclodipyranyl coumarins and the anti-hiv and anti-tuberculosis uses thereof |
| CN102732474A (en) * | 2012-05-21 | 2012-10-17 | 中山大学 | Compound for inhibiting mycobacterium tuberculosis, screening method and uses thereof |
Non-Patent Citations (2)
| Title |
|---|
| PRIYA RAJDEV，等: "Simultaneous binding of anti-tuberculosis and anti-thrombosis drugs to a human transporter protein: A FRET study", 《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY》, vol. 103, no. 2, 5 March 2011 (2011-03-05), pages 153 - 158, XP028189788, DOI: doi:10.1016/j.jphotobiol.2011.02.023 * |
| 魏美燕 等: "南海海洋真菌Penicillium sp.(386#)次级代谢产物再研究", 《中山大学学报》, vol. 49, no. 4, 31 July 2010 (2010-07-31), pages 77 - 80 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104311526A (en) * | 2014-09-13 | 2015-01-28 | 中山大学 | Marine fungus-derived dinaphthalene derivatives and their preparation method and use in tuberculosis resistance |
| CN104311525A (en) * | 2014-09-13 | 2015-01-28 | 中山大学 | Use of marine fungus-derived Azaphilone compound in preparation of antituberculosis drugs |
| CN104311526B (en) * | 2014-09-13 | 2016-03-23 | 中山大学 | The dinaphthalene analog derivative in thalassiomycetes source and preparation method thereof and the application in tuberculosis |
| CN108441526A (en) * | 2017-02-04 | 2018-08-24 | 扬州大学 | A method of mass producing penicilone class compounds using marine fungi |
| CN108441526B (en) * | 2017-02-04 | 2021-06-22 | 扬州大学 | Method for large-scale production of penicilione compounds by using marine fungi |
| CN107721972A (en) * | 2017-08-25 | 2018-02-23 | 中山大学 | The benzophenone analog derivative in a kind of marine fungi source and preparation method thereof and the application in antituberculotic is prepared |
| CN107721972B (en) * | 2017-08-25 | 2019-06-07 | 中山大学 | The benzophenone analog derivative in a kind of marine fungi source and preparation method thereof and preparing the application in antituberculotic |
| CN109836395A (en) * | 2017-11-29 | 2019-06-04 | 扬州蓝色生物医药科技有限公司 | A kind of o-trifluoromethyl phenoxy acetamide base thiazole sulfonamide MptpB inhibitor |
| CN109836396A (en) * | 2017-11-29 | 2019-06-04 | 扬州蓝色生物医药科技有限公司 | A kind of novel thiazole sulfamide compound and its application as antituberculotic |
| CN109836395B (en) * | 2017-11-29 | 2020-08-04 | 扬州蓝色生物医药科技有限公司 | O-trifluoromethyl phenoxyacetamido thiazole sulfonamide MptpB inhibitor |
| CN109836396B (en) * | 2017-11-29 | 2020-08-04 | 扬州蓝色生物医药科技有限公司 | Novel thiazole sulfonamide compound and application thereof as antituberculosis drug |
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