CN1403469A - Antineoplastic compound and its prepn and medicinal use - Google Patents
Antineoplastic compound and its prepn and medicinal use Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title abstract description 10
- 230000000118 anti-neoplastic effect Effects 0.000 title abstract description 3
- 241000233866 Fungi Species 0.000 claims abstract description 25
- 241000196324 Embryophyta Species 0.000 claims abstract description 14
- 238000000605 extraction Methods 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 238000012360 testing method Methods 0.000 claims description 7
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- 238000000855 fermentation Methods 0.000 claims description 6
- 230000004151 fermentation Effects 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 229940041181 antineoplastic drug Drugs 0.000 claims description 5
- 238000010828 elution Methods 0.000 claims description 5
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- 238000001914 filtration Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
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- 239000001888 Peptone Substances 0.000 claims description 3
- 108010080698 Peptones Proteins 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 229940041514 candida albicans extract Drugs 0.000 claims description 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 claims description 3
- 238000013375 chromatographic separation Methods 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 235000019319 peptone Nutrition 0.000 claims description 3
- 238000011218 seed culture Methods 0.000 claims description 3
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- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 229960001866 silicon dioxide Drugs 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000012138 yeast extract Substances 0.000 claims description 3
- 235000014666 liquid concentrate Nutrition 0.000 claims description 2
- 239000013028 medium composition Substances 0.000 claims description 2
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- 238000011160 research Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
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- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
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- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
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- 239000002953 phosphate buffered saline Substances 0.000 description 2
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- 231100000167 toxic agent Toxicity 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241001019659 Acremonium <Plectosphaerellaceae> Species 0.000 description 1
- 241001327634 Agaricus blazei Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 240000003793 Rhizophora mangle Species 0.000 description 1
- 241000864405 Russula rosacea Species 0.000 description 1
- 241000228417 Sarocladium strictum Species 0.000 description 1
- 241001346815 Spongia officinalis Species 0.000 description 1
- 241000222355 Trametes versicolor Species 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
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- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
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- 230000002526 effect on cardiovascular system Effects 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
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- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to compound ergosta-8(9),22-diene-3,5,6,7-tetraol, its extraction and separation process from marine plant fungus No.2059 with preservation number of CCTCCM202030 and its application is preparing antineoplastic medicine.
Description
Technical field
The present invention relates to a kind of compound 3 β, 5 α, 6 β with anti-tumor activity, 7 α-tetrahydroxy-8 (9), 22 Z-diene ergot alkane [ergosta-8 (9), 22-diene-3,5,6,7-tetraol (3 β, 5 α, 6 β, 7 α 22Z), are designated hereinafter simply as compd A] and preparation method thereof and in the application of preparation in the antitumor drug.
Background technology
(penicillin) introduced medical science since penicillin, just indicates that the antibiotic epoch of fungi begin.In in the past 60 years, found the natural product of a large amount of structure uniquenesses from the land fungi, wherein a lot of as medicine or as the potential instruments of biological medicine development.The meta-bolites of fungi is much used as microbiotic clinically as the abundant source of medicine, and a large amount of studies show that, the meta-bolites of fungi also has other pharmaceutical use, as antitumor, and treatment cardiovascular disorder, immunomodulator, enzyme inhibitors etc.Because unique pathways metabolism and genetic background, the meta-bolites that can provide the Lu Sheng fungi to provide are provided for the singularity of ocean environment, thalassiomycetes.From thalassiomycetes, found the compound of some structure uniquenesses in the world, have respectively antibiotic, antiviral, the activity of antitumor and cardiovascular aspect.For example, in July, 1945, Giuseppe Brotzu finds that cephalosporium acremonium (Cephalospoiun acremonium) has the activity of the growth that suppresses gram positive bacterium and gram negative bacterium, obtains multiple antibiotic, i.e. cynnematin after separate.Five more than ten years went over, and cynnematin still is extensive use of clinically.From fungi screening, to semi-synthetic structure of modification, range of product has reached kind more than 200 at present, and output accounts for more than 60% of microbiotic output in the world, can be rated as the up-and-coming youngster.Are other some examples seen article " the Marine fungi-a profileresource of biologically active natural products of Kerstin Liberra in addition? " [Pharmazie 50 (1995), H.9:583], the research of this respect has been the trend of accelerated development since the eighties in the world.The domestic a collection of new active substance (Lin YC et al Tetrahedron2000, Lin YC et al Tetrahedron Letters, 2000, Lin YC et al J.Org.Chem.2001) of from thalassiomycetes, also finding.
The bibliographical information of relevant tetrahydroxy sterol, also considerably less at present.From land wood-decay fungi Polyporus versicolor, the sporophore of fungi Agaricus blazei and sponge Spongia officinali[A.Migliuolo, et al.J.Nat.Prod., 1990,53,1414-1424] and Chinese bitter russule Russula rosacea in [Wang Huaibin etc., herbal medicine, 1994,25 (7), 342-343] be separated to a kind of tetrahydroxy sterol Ergosta-7,22-diene-3,5,6,9-tetraol (3 β, 5 α, 6 β, 9 α).T.Ishizuka etc. are separated to 18 phytosterin compounds from the sporophore of fungus G rifola frondosa, two tetrahydroxy sterol Ergosta-8 (9) are wherein arranged, 22-diene-3,5,6,7-tetraol (3 β, 5 α, 6 β, 7 α, 22E) and Ergosta-8 (14), 22-diene-3,5,6,7-tetraol (3 β, 5 α, 6 β, 7 α, 22E) [T.Ishizuka, et al.Chem.Pharm.Bull., 1997,45 (11), 1756-1760].According to bibliographical information, the tetrahydroxy sterol all has cytotoxic activity basically, but the trihydroxy-sterol does not much have cell toxicant, the existence of hydroxyl and the relation between the cytotoxicity, the tetrahydroxy sterol mechanism of action etc. are all not clear now, and these also all are worth further research.
Plant endogenous property fungi (endophytic fungi) lives in the tissue of higher plant, also comparatively lacks for the research of the secondary metabolites of endogenous fungi.The endogenous fungi is of a great variety at a conservative estimate, and nearly 1.5 * 10
6Kind because quantity is huge, and and other biology between ecological relationship closely, make this class fungi become potential and have the source that produces abundant secondary metabolites.At present domestic other unit yet there are no report to the research of the secondary metabolites of the endogenous fungi that grows in ocean environment.
Summary of the invention
The object of the present invention is to provide a kind of new new compound and from the method for marine plant endogenetic fungus extraction separation with potential pharmaceutical use, and the purposes of this compound in the preparation antitumor drug.
The compounds of this invention A is shown in the following structural:
Compd A of the present invention can be from the marine plant fungi, for example extraction separation and obtaining in the thalline of the endogenetic fungus 2059 of ocean, South Sea mangrove forest Castaniopsis fissa (hereinafter referred to as marine plant fungi 2059).
The used marine plant fungi 2059 of the present invention has been preserved in Chinese typical culture collection center (CCTCC, China, Wuhan University are in the school), and preserving number is CCTCC №: M202030, and preservation day is on August 3rd, 2002.
The preparation method of The compounds of this invention A may further comprise the steps:
A. the seed culture of marine plant fungi CCTCC M202030:
Select PDA (potato dextro se agar) substratum for use, it consists of: potato 200g, glucose 20g, agar 20g, water 1L; Make the test tube slant, the picking bacterial strain inserts the inclined-plane, cultivates 5-7 days for 25-28 ℃;
B. the fermentation culture of marine plant fungi CCTCC M202030:
The fermention medium composition proportion is by weight: glucose 5-15, yeast extract 0.5-1.5, peptone 1-3, thick sea salt 30-50, water 1000; Cultured bacterial strain in the inclined-plane is chosen into fermention medium, left standstill the 1-2 month in room temperature 25-30 ℃;
C. with above-mentioned cultured filtering fermentation liquor, collect thalline, dry;
D. thalline at room temperature soaks with methyl alcohol, and united extraction liquid concentrates and obtains general extractive;
E. use the acetic acid ethyl dissolution extract, solute carries out chromatographic separation in silicagel column, with petroleum ether-ethyl acetate-methyl alcohol gradient elution;
F. collect the elution fraction that petroleum ether-ethyl acetate (1: 3) obtains, further silica gel column chromatography is an eluent with chloroform-methanol (7: 1), and purifying obtains white amorphism solid, is required compd A.
Evidence of the present invention, compd A can suppress the growth of tumor cell line, detects in the anti-tumor activity test medium lethal dose IC of compd A in the MTT reduction method that with human hepatoma cell strain and National People's Congress's sclc cell line is target cell
50Be respectively 8.445 and 5.03 μ g/ml.Show that compd A can be used for preparing antitumor drug.
Embodiment
The invention will be further described below in conjunction with embodiment.Embodiment 1: the preparation of compd A
A. the seed culture of marine plant fungi CCTCC M202030:
Bacterial classification is a substratum with PDA, consists of: potato 200g, glucose 20g, agar 20g, water 1L.Make the test tube slant, the picking bacterial strain inserts the inclined-plane, cultivates after 7 days in 4 ℃ of preservations for 25-28 ℃.
B. the fermentation culture of marine plant fungi CCTCC M202030:
Fermention medium consists of: glucose 10g, yeast extract 1g, peptone 2g, thick sea salt 40g, water 1L; Cultured bacterial strain in the inclined-plane is chosen into fermention medium, left standstill in room temperature 25-28 ℃ and cultivated 1 month;
C. with above-mentioned cultured filtering fermentation liquor, collect thalline, dry;
D. thalline at room temperature soaked 7 days with methyl alcohol, and lixiviate is 3 times altogether, and united extraction liquid, rotary evaporation concentrate and obtains general extractive;
E. use the acetic acid ethyl dissolution extract, solute carries out chromatographic separation in silicagel column, with petroleum ether-ethyl acetate-methyl alcohol gradient elution;
F. collect the component that is obtained by petroleum ether-ethyl acetate (1: 3) wash-out, further silica gel column chromatography is an eluent with chloroform-methanol (7: 1), and purifying obtains white amorphism solid chemical compound A.
The testing data of compd A:
m.p.145～150℃。Ultimate analysis (w%, C
28H
46O
4): C 75.54, and H 10.22, and N 0.000; Calculated value: C 75.34, H 10.21, and N 0.000; IR υ/cm
-1(KBr): 3423,2959,2872,1668,1634,1461,1378,1276,1158,1067,969,915,878,805,733.APCI-MS:429[M-H
2O+H]
+, 411[M-2H
2O+H]
+, 393[M-3H
2O+H]
+, 375[M-4H
2O+H]
+, 267,251,187,171,131,105 etc.The NMR experimental data of compd A is as shown in table 1.Embodiment 2:MTT reduction method detection compound A anti-tumor activity test
1. material:
1.1 four Cuo salt (MTT): with phosphate buffered saline buffer (PBS) dissolving MTT (3-(4.5-dimethythiazol-z-yl) 2 of 0.01mol/L, 5-diphenytetrazolium bromide, SIGMA) final concentration 5mg/ml, filtration sterilization, 4 ℃ keep in Dark Place after the packing.
1.2MTT the sodium laurylsulfonate (SDS of the preparation of lysate: 80g, Huamei Bio-Engrg Co.) is dissolved in the N-N-dimethyl formamide (Beijing Chemical Plant) of 200ml, the heating in water bath hydrotropy adds 200ml distilled water, mixes with 1N hydrochloric acid (1: 1) with 80% acetate and transfers pH to 4.7.
1.3 cell strain is selected for use: human normal cell line strain (L-02), human hepatoma cell strain (Bel-7402) and National People's Congress's sclc cell line (NCI4460).
2. operation steps:
A. single cell suspension is inoculated in 96 orifice plates (with the RPMI-1640 basic medium with cell dilution to 3 * 10
4/ ml, every hole adds 200 μ l
The cell that dilution is good), 37 ℃, 5%CO
2, cultivated 24 hours under the saturated humidity; Every group of four parallel samples;
B. remove substratum, get new preparation substratum and prepare cancer therapy drug (compd A) solution by series concentration, every hole 200 μ l cultivate 48
Hour;
C. every hole adds the MTT 20 μ l of 2mg/ml, hatches 4 hours;
D. nutrient solution (as far as possible fully) in the sucking-off hole adds DMSO liquid (150 μ l/ hole), vibrates 10 minutes, and crystallisate is fully dissolved;
E. microplate reader detects each hole OD value, (λ=570nm);
F. draw the cell viability graphic representation, obtain IC
50Value.
Test-results is as shown in table 2.The test-results explanation, compd A has stronger cell toxicant, and its toxicity has certain selectivity to normal cell and cancer cells; Compd A can be used for preparing antitumor drug.
The NMR data of table 1 compd A (Acetone-d6, TMS, ppm) carbon item δ C DEPT δ H HMBC
1H-
1HCOSY1 31.1 CH
21.54 1.13,1.57 1.73
1.73 1.542 31.9 CH
2 1.57 1.85，3.76
1.85 1.573 68.6 CH 3.76 1.73，2.13 1.57，2.134 40.2 CH
2 1.32 2.13
2.13 1.32，3.765 64.9 C 1.13，1.32，1.736 67.5 CH 4.20(brd，10.0Hz) 3.13 3.13，3.347 63.3 CH 3.13(d，2.5Hz) 4.208 128.2 C 2.22，3.139 134.3 C 1.13，1.94，2.02，2.2210 39.0 C11 24.4 CH
2 1.94 1.38，2.01，2.02
2.02 1.38，1.94，2.0112 36.8 CH
2 1.38 0.64，1.94
2.0113 42.8 C 0.64，1.22，2.18，2.2214 50.8 CH 2.22 0.64，2.05 1.3215 30.0 CH
2 1.32 1.22 2.05，2.18
2.05 1.3216 24.2 CH
2 2.18 1.22，1.3217 54.6 CH 1.22 0.64，1.05 1.32，2.10，2.1818 11.7 CH
3 0.64(s) 1.22，1.3819 22.8 CH
3 1.13(s)20 41.3 CH 2.10 0.64，1.05，1.22 1.05，1.22，1.3221 21.4 CH
3 1.05(d，6.5Hz) 2.1022 136.8 CH 5.24(d，6.0Hz) 1.05，1.88，2.1023 132.6 CH 5.25(d，6.0Hz) 0.94，1.88，2.1024 43.7 CH 1.88 0.84，0.86，0.94 0.9425 18.1 CH
3 0.94(d，7.0Hz) 1.8826 33.8 CH 1.99 0.84，0.86，0.9427 20.3 CH
3 0.86(d，8.0Hz) 0.84 0.8428 20.0 CH
3 0.84(d，6.5Hz) 0.86 0.863-OH OH 3.68(d，5.0Hz)5-OH OH 2.776-OH OH 3.34(d，10.0Hz)7-OH OH 2.77
The cell toxicity test result of table 2 A tests cell normal liver cell strain human hepatoma cell strain National People's Congress sclc cell line
L-02 Bel-7402 NCI4460IC
50(μg/ml) 13.621 8.445 5.03
Claims (3)
1. the compd A shown in the following structural formula:
2. the preparation method of the described compd A of claim 1 is characterized in that this method may further comprise the steps:
A. the seed culture of marine plant fungi CCTCC M202030:
Select the PDA substratum for use, it consists of: potato 200g, glucose 20g, agar 20g, water 1L; Make the test tube slant, the picking bacterial strain inserts the inclined-plane, cultivates 5-7 days for 25-28 ℃;
B. the fermentation culture of marine plant fungi CCTCC M202030:
The fermention medium composition proportion is by weight: glucose 5-15, yeast extract 0.5-1.5, peptone 1-3, thick sea salt 30-50, water 1000; Cultured bacterial strain in the inclined-plane is chosen into fermention medium, left standstill the 1-2 month in room temperature 25-30 ℃;
C. with above-mentioned cultured filtering fermentation liquor, collect thalline, dry;
D. thalline at room temperature soaks with methyl alcohol, and united extraction liquid concentrates and obtains general extractive;
E. use the acetic acid ethyl dissolution extract, solute carries out chromatographic separation in silicagel column, with petroleum ether-ethyl acetate-methyl alcohol gradient elution;
F. collect the elution fraction that petroleum ether-ethyl acetate (1: 3) obtains, further silica gel column chromatography is an eluent with chloroform-methanol (7: 1), and purifying obtains white amorphism solid, is required compd A.
3. the described compd A of claim 1 is used to prepare antitumor drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021347115A CN1158298C (en) | 2002-09-12 | 2002-09-12 | Antineoplastic compound and its prepn and medicinal use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021347115A CN1158298C (en) | 2002-09-12 | 2002-09-12 | Antineoplastic compound and its prepn and medicinal use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1403469A true CN1403469A (en) | 2003-03-19 |
| CN1158298C CN1158298C (en) | 2004-07-21 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005037813A1 (en) * | 2003-10-21 | 2005-04-28 | Sun Yat-Sen University | A compound, the preparation and the use thereof |
| CN100360515C (en) * | 2004-04-09 | 2008-01-09 | 中国科学院上海药物研究所 | Lingshui alcohol with anti-cancer activity, its preparation and use |
| CN100389202C (en) * | 2005-07-25 | 2008-05-21 | 厦门大学 | Fermentation substrate of antitumour compound fungus epoxydiester |
| CN101255103B (en) * | 2008-02-27 | 2011-05-11 | 厦门大学 | Preparation method of marine penicillium antitumor reactive compound and utilization thereof |
| CN110437192A (en) * | 2019-07-31 | 2019-11-12 | 暨南大学 | A kind of compound, composition, preparation method and its usage for extracting from Spongia and belonging to sponge |
-
2002
- 2002-09-12 CN CNB021347115A patent/CN1158298C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005037813A1 (en) * | 2003-10-21 | 2005-04-28 | Sun Yat-Sen University | A compound, the preparation and the use thereof |
| CN100360515C (en) * | 2004-04-09 | 2008-01-09 | 中国科学院上海药物研究所 | Lingshui alcohol with anti-cancer activity, its preparation and use |
| CN100389202C (en) * | 2005-07-25 | 2008-05-21 | 厦门大学 | Fermentation substrate of antitumour compound fungus epoxydiester |
| CN101255103B (en) * | 2008-02-27 | 2011-05-11 | 厦门大学 | Preparation method of marine penicillium antitumor reactive compound and utilization thereof |
| CN110437192A (en) * | 2019-07-31 | 2019-11-12 | 暨南大学 | A kind of compound, composition, preparation method and its usage for extracting from Spongia and belonging to sponge |
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| Publication number | Publication date |
|---|---|
| CN1158298C (en) | 2004-07-21 |
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