CN101836977B - Extract of Morus australis Poir. and antibacterial application of Kuwanon H compound - Google Patents
Extract of Morus australis Poir. and antibacterial application of Kuwanon H compound Download PDFInfo
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- CN101836977B CN101836977B CN2009101194643A CN200910119464A CN101836977B CN 101836977 B CN101836977 B CN 101836977B CN 2009101194643 A CN2009101194643 A CN 2009101194643A CN 200910119464 A CN200910119464 A CN 200910119464A CN 101836977 B CN101836977 B CN 101836977B
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- 239000000284 extract Substances 0.000 title claims abstract description 42
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 36
- DKBPTKFKCCNXNH-YWUCGUBVSA-N Kuwanon H Natural products CC(C)=CCC1=C(O)C=CC(C(=O)[C@@H]2[C@@H](C=C(C)C[C@H]2C=2C(=CC(O)=CC=2)O)C=2C3=C(C(C(CC=C(C)C)=C(O3)C=3C(=CC(O)=CC=3)O)=O)C(O)=CC=2O)=C1O DKBPTKFKCCNXNH-YWUCGUBVSA-N 0.000 title claims abstract description 11
- -1 Kuwanon H compound Chemical class 0.000 title abstract description 9
- 240000009253 Morus australis Species 0.000 title abstract description 9
- 235000006723 Morus australis Nutrition 0.000 title abstract description 9
- 241000191967 Staphylococcus aureus Species 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 26
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims description 26
- 229960003085 meticillin Drugs 0.000 claims description 13
- 239000003643 water by type Substances 0.000 claims description 13
- 229960000723 ampicillin Drugs 0.000 claims description 10
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 10
- 229960003276 erythromycin Drugs 0.000 claims description 9
- 239000006210 lotion Substances 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 208000035143 Bacterial infection Diseases 0.000 claims description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 241000192125 Firmicutes Species 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- DKBPTKFKCCNXNH-QXGWMLRCSA-N kuwanone H Chemical compound CC(C)=CCC1=C(O)C=CC(C(=O)[C@@H]2[C@H](C=C(C)C[C@H]2C=2C(=CC(O)=CC=2)O)C=2C3=C(C(C(CC=C(C)C)=C(O3)C=3C(=CC(O)=CC=3)O)=O)C(O)=CC=2O)=C1O DKBPTKFKCCNXNH-QXGWMLRCSA-N 0.000 claims description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 230000008676 import Effects 0.000 claims description 2
- 240000000249 Morus alba Species 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 235000008708 Morus alba Nutrition 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
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- 206010041925 Staphylococcal infections Diseases 0.000 description 8
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 241000218213 Morus <angiosperm> Species 0.000 description 5
- 239000000084 colloidal system Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- APPXYONGBIXGRO-UHFFFAOYSA-N kuwanon G Natural products OC1=CC(O)=C2C(=O)C(CC=C(C)C)=C(C=3C(=CC(O)=CC=3)O)OC2=C1C1C=C(C)CC(C=2C(=CC(O)=CC=2)O)C1C(=O)C1=CC=C(O)C=C1O APPXYONGBIXGRO-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
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- 230000001077 hypotensive effect Effects 0.000 description 4
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- APPXYONGBIXGRO-AIQWNVMPSA-N kuwanone G Chemical compound O=C([C@H]1[C@@H](CC(C)=C[C@@H]1C1=C2OC(=C(C(C2=C(O)C=C1O)=O)CC=C(C)C)C=1C(=CC(O)=CC=1)O)C=1C(=CC(O)=CC=1)O)C1=CC=C(O)C=C1O APPXYONGBIXGRO-AIQWNVMPSA-N 0.000 description 4
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- 238000012360 testing method Methods 0.000 description 4
- ZXTQHAMOONDJDJ-YTAXAHCSSA-N (2s)-6-[(1s,5r,6s)-6-(2,4-dihydroxybenzoyl)-5-(2,4-dihydroxyphenyl)-3-(4-methylpent-3-enyl)cyclohex-2-en-1-yl]-2-(2,5-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydrochromen-4-one Chemical compound C1([C@H]2[C@@H]([C@H](C=C(C2)CCC=C(C)C)C=2C(=C3C(=O)C[C@H](OC3=CC=2O)C=2C(=CC=C(O)C=2)O)O)C(=O)C=2C(=CC(O)=CC=2)O)=CC=C(O)C=C1O ZXTQHAMOONDJDJ-YTAXAHCSSA-N 0.000 description 3
- 208000001953 Hypotension Diseases 0.000 description 3
- 241000301120 Morus lhou Species 0.000 description 3
- WTGKDESIYCVAOP-NPPPIGHJSA-N Mulberrofuran C Natural products O=C([C@@H]1[C@@H](c2c(O)cc(-c3oc4c(c3)ccc(O)c4)cc2O)C=C(C)C[C@@H]1c1c(O)cc(O)cc1)c1c(O)cc(O)cc1 WTGKDESIYCVAOP-NPPPIGHJSA-N 0.000 description 3
- VYCKCQBOVSSJSK-ANWKEMATSA-N Sanggenon G Natural products O=C([C@H]1[C@H](c2c(O)c3C(=O)C[C@H](c4c(O)cc(O)cc4)Oc3cc2O)C=C(CC/C=C(\C)/C)C[C@@H]1c1c(O)cc(O)cc1)c1c(O)cc(O)cc1 VYCKCQBOVSSJSK-ANWKEMATSA-N 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
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- 229930184898 kuwanon Natural products 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- WCJPAQJEARHLGS-KEBDBYFISA-N 5-[7-[(2e)-3,7-dimethylocta-2,6-dienyl]-6-hydroxy-1-benzofuran-2-yl]-4-(3-methylbut-2-enyl)benzene-1,3-diol Chemical compound O1C=2C(C/C=C(C)/CCC=C(C)C)=C(O)C=CC=2C=C1C1=CC(O)=CC(O)=C1CC=C(C)C WCJPAQJEARHLGS-KEBDBYFISA-N 0.000 description 2
- KEIIIPKLVSSAEI-UHFFFAOYSA-N Albanin A Chemical group O1C2=CC(O)=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC=C(O)C=C1O KEIIIPKLVSSAEI-UHFFFAOYSA-N 0.000 description 2
- 102000003850 Dipeptidase 1 Human genes 0.000 description 2
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- DBUNRZUFILGKHP-UHFFFAOYSA-N Kuwanon A Natural products C1=CC(C)(C)OC2=C1C(O)=CC=C2C1=C(CC=C(C)C)C(=O)C2=C(O)C=C(O)C=C2O1 DBUNRZUFILGKHP-UHFFFAOYSA-N 0.000 description 2
- 244000293610 Morus bombycis Species 0.000 description 2
- 235000006721 Morus bombycis Nutrition 0.000 description 2
- WCJPAQJEARHLGS-JMIUGGIZSA-N Mulberrofuran D Natural products Oc1c(C/C=C(\C)/C)c(-c2oc3c(C/C=C(\CC/C=C(\C)/C)/C)c(O)ccc3c2)cc(O)c1 WCJPAQJEARHLGS-JMIUGGIZSA-N 0.000 description 2
- 208000025157 Oral disease Diseases 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000012531 culture fluid Substances 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 238000003113 dilution method Methods 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
- 208000030194 mouth disease Diseases 0.000 description 2
- WTGKDESIYCVAOP-UNTHUGQZSA-N mulberrofuran C Chemical compound C1([C@H]2[C@@H]([C@@H](C=C(C2)C)C=2C(=CC(=CC=2O)C=2OC3=CC(O)=CC=C3C=2)O)C(=O)C=2C(=CC(O)=CC=2)O)=CC=C(O)C=C1O WTGKDESIYCVAOP-UNTHUGQZSA-N 0.000 description 2
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- 229920005989 resin Polymers 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229930192840 Albanin Natural products 0.000 description 1
- MQQJRRDEGVHDBJ-UHFFFAOYSA-N Albanin F Natural products CC1CC(C(C(=O)c2ccc(O)cc2O)C(=C1)c3c(O)cc(O)c4C(=O)C(=C(Oc34)c5ccc(O)cc5O)CC=C(C)C)c6ccc(O)cc6O MQQJRRDEGVHDBJ-UHFFFAOYSA-N 0.000 description 1
- HDHRTQZSBFUBMJ-UHFFFAOYSA-N Artonin E Natural products O1C2=C3C=CC(C)(C)OC3=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC(O)=C(O)C=C1O HDHRTQZSBFUBMJ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- LTSRSDARASWSQF-UHFFFAOYSA-N Kuwanol A Natural products CC1=CC2C3C(C1)c4ccc(O)cc4OC3(Oc5cc(C=Cc6ccc(O)cc6O)ccc25)c7ccc(O)cc7O LTSRSDARASWSQF-UHFFFAOYSA-N 0.000 description 1
- APPXYONGBIXGRO-FPQPQGOJSA-N Kuwanone G Natural products O=C([C@@H]1[C@H](c2c(O)cc(O)c3C(=O)C(C/C=C(\C)/C)=C(c4c(O)cc(O)cc4)Oc23)C=C(C)C[C@H]1c1c(O)cc(O)cc1)c1c(O)cc(O)cc1 APPXYONGBIXGRO-FPQPQGOJSA-N 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000218231 Moraceae Species 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 229930182734 Sanggenon Natural products 0.000 description 1
- WTGKDESIYCVAOP-CAHKVJEUSA-N [(1s,2s,6r)-2-[2,6-dihydroxy-4-(6-hydroxy-1-benzofuran-2-yl)phenyl]-6-(2,4-dihydroxyphenyl)-4-methylcyclohex-3-en-1-yl]-(2,4-dihydroxyphenyl)methanone Chemical compound C1([C@H]2[C@@H]([C@H](C=C(C2)C)C=2C(=CC(=CC=2O)C=2OC3=CC(O)=CC=C3C=2)O)C(=O)C=2C(=CC(O)=CC=2)O)=CC=C(O)C=C1O WTGKDESIYCVAOP-CAHKVJEUSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
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- 230000035619 diuresis Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
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- 238000011049 filling Methods 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- LLROUPDIAXFXDY-UHFFFAOYSA-N moracenin B Natural products OC1=CC(O)=C2C(=O)C(CC=C(C)C)=C(C=3C(=CC(O)=CC=3)O)OC2=C1C1C=C(C)CC(C(=O)C=2C(=CC(O)=CC=2)O)C1C1=CC=C(O)C=C1O LLROUPDIAXFXDY-UHFFFAOYSA-N 0.000 description 1
- XFFOMNJIDRDDLQ-UHFFFAOYSA-N morusin Chemical compound O1C2=C3C=CC(C)(C)OC3=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC=C(O)C=C1O XFFOMNJIDRDDLQ-UHFFFAOYSA-N 0.000 description 1
- WUBUWBUVAKMGCO-UHFFFAOYSA-N morusin Natural products CC(=CCC1=C(Cc2c3C=CC(C)(C)Oc3cc(O)c2C1=O)c4ccc(O)cc4O)C WUBUWBUVAKMGCO-UHFFFAOYSA-N 0.000 description 1
- OPMAIQOGIRTPOM-UHFFFAOYSA-N mulberrofuran J Natural products CC1=CC(C(C(C1)c2ccc(O)cc2O)C(=O)c3ccc(O)cc3O)c4c(O)cc5oc(cc5c4O)c6cccc(O)c6 OPMAIQOGIRTPOM-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
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- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an extract made of Morus australis Poir. root bark and antibacterial application of Kuwanon H compound which is separated from the extract and has a structure as shown in a formula (I).
Description
Technical field
The invention relates to a kind of preparation from childhood mulberry (Morus australis Poir.) root bark extract and by the antibacterial application of the Kuwanon H chemical compound of separating in the extract.
Background technology
Japan Patent JP10-007555 has disclosed from the Morus plant; Morus bombycis Koidz for example; Morus alba L., the isolated mulberrofuran C of the bark extract of Morus lhou Koidz, D, and G, five kinds of chemical compounds of kuwanol A and sanggenone G; And antibacterial application, for example staphylococcus aureus, anti-methicillin staphylococcus aureus (MRSA).
Japan Patent JP56-123979 has disclosed from the Morus plant, Morus bombycis Koidz for example, and Morus alba L., the root bark extract of Morus lhou Koidz isolate kuwanon G and two kinds of chemical compounds of H, and the blood pressure lowering purposes.
Summary of the invention
A main purpose of the present invention is to provide a kind of have the kuwanon H chemical compound of formula (I) structure or the antibacterial application of medical acceptable salt therefrom.
Above-mentioned antibacterial application of the present invention comprises a kind of kuwanon of comprising H chemical compound or medical acceptable salt therefrom medical composition as effective ingredient; A kind of kuwanon of use H chemical compound or medical acceptable salt therefrom are made an antibiotic medicine as effective ingredient purposes; And a kind of method of treating bacterial infection patients, comprise kuwanon H chemical compound or the medical acceptable salt therefrom of this patient being bestowed a treatment effective dose.
Another object of the present invention is to provide the antibacterial application of extract of the root bark preparation of a kind of mulberry from childhood (Morus australis Poir.).
The antibacterial application of extract of the present invention comprises a kind of medical composition that comprises this extract as effective ingredient; A kind of purposes of using this extract to make an antibiotic medicine as effective ingredient; And a kind of method of treating bacterial infection patients, comprise this extract of this patient being bestowed a treatment effective dose.
Of the present invention antibiotic from being meant treatment in broad terms because of any discomfort (disorder) that bacterial infection caused, the growth that then is meant the inhibition antibacterial of narrow sense.
Cortex Mori (" Sang-Bai-Pi ") is a kind of Chinese medicine, and it is the root bark of exsiccant mulberry Morus alba L., and its purposes has antiinflammatory, diuresis, antitussive etc.Open-air Morus alba L. is actually rare in Taiwan, and the quantity of little mulberry (Morus australis Poir.) is a lot.So the extract that this case inventor trial is prepared industrial utilization from little mulberry reaches the chemical compound of from this extract, isolating industrial utilization.
The invention provides a kind of antibacterial application of KuwanonH chemical compound, the chemical compound of use formula (I) structure or medical acceptable salt therefrom are made the medicine of treatment bacterial infection as active ingredient:
Preferable, this antibacterial is a gram positive bacteria.
Preferable, this antibacterial is staphylococcus aureus or streptococcus pneumoniae.Better, this antibacterial is a staphylococcus aureus.Best, this antibacterial is an anti-methicillin staphylococcus aureus (MRSA).Better, this antibacterial is a streptococcus pneumoniae.Best, this antibacterial is anti-erythromycin and Ampicillin (Ampicillin) streptococcus pneumoniae.
The present invention also provides the antibacterial application of the extract of a kind of little mulberry; Use extracts the medicine that the extract of mulberry (Morus australis Poir.) root bark is from childhood made the treatment bacterial infection; Wherein this antibacterial is a gram positive bacteria, for example staphylococcus aureus or streptococcus pneumoniae.Preferable, this antibacterial is a staphylococcus aureus.Better, this antibacterial is anti-methicillin staphylococcus aureus.Better, this antibacterial is a streptococcus pneumoniae.Best, this antibacterial is anti-erythromycin and Ampicillin streptococcus pneumoniae.
One suitable method for preparing of extract of the present invention comprises the following step:
A) little mulberry (Morus australis Poir.) root bark is with a polar solvent extract;
B) concentration step extract a);
C) concentrate with step b) imports a reverse-phase chromatography tubing string and washes this tubing string with first-class washing liquid and second flowing lotion stream in regular turn; With the eluat that obtains first-class washing liquid and the eluat of second flowing lotion; Wherein the polarity of this first-class washing liquid is about 50 weight % ethanol waters, and the polarity of this second flowing lotion is about 95 weight % ethanol waters; And
D) collect the eluat of this second flowing lotion, and volatilization removes solvent wherein.
Preferable, this extract has comprised the chemical compound of Sanggenon G of chemical compound and tool following formula (II) structure of above-mentioned formula (I) structure:
Preferable, this extract comprises the chemical compound of 1～5% formula (I) structure and the chemical compound of 1～5% formula (II) structure, is benchmark with the weight of this extract.Better, this extract comprises the chemical compound of about 3.7% formula (I) structure and the chemical compound of about 2.3% formula (II) structure, is benchmark with the weight of this extract.
Preferable, the first-class washing liquid of step c) is 50 weight % ethanol waters, and this second flowing lotion is 95 weight % ethanol waters.
Preferable, the polar solvent of step a) is water or 95 weight % ethanol waters.Better, the polar solvent of step a) is 95 weight % ethanol waters.
The present invention will further be understood by following examples, and they are only as the usefulness of explanation, and not exclusively be used to limit the scope of the invention.
The specific embodiment
Embodiment 1: the preparation of extract EX-1
Weigh exsiccant little mulberry (Morus australis Poir., Moraceae) root bark 100g, pulverize the back and add 95 weight % ethanol water 1000ml (10 times of extractants (v/w)) and place round-bottomed flask, with heat packs reflux 1 hour.Screen cloth and No. 2 filter paper filterings with 350 meshes.Residue repeats above-mentioned reflux and filtration step once again.Merge filtrating twice, get wherein its dry powder amount of sub-fraction survey, the dry powder that calculates whole filtratings heavily is 10.21g (thick extract extraction yield: 10.21 weight %).Whole filtrating is concentrated into 1/10 of former weight, adds and wait water gaging Hui Rong, again with its filling polystyrene adsorption resin (DiaionHP20gel) of packing into (extract dry powder/resin=1/30 slightly, reverse-phase chromatography tubing string w/w).Use 2 times of colloid gap bed volumes (Bed volume=600ml); The 95 weight % ethanol waters of 50 weight % ethanol waters and 1200ml that are 1200ml flow with 50 weight % ethanol waters and 95 weight % ethanol waters in regular turn and wash as mobile phase.Collect the eluat of this 95 weight % ethanol water, and the code name that obtains 2.73g after being dried is the extract of EX-1.The EX-1 productive rate of tubing string chromatography: 26.7 weight %.The productive rate that EX-1 extracts from former dry root bark is 2.73 weight %.
Embodiment 2: the further separation of extract EX-1
Get EX-12g, after dissolving fully with 10ml methanol, add the 10ml pure water and acutely rock, have deposition to form, again with centrifugal 15 minutes of centrifuge (rotating speed 10000rpm) with hands.Repeat above-mentioned dissolving, deposition and centrifugation step totally six times.
Six times centrifugal resulting liquid is evaporated to dried (1.3g) by merging.(Silica Gel 60) further separates this dry powder (dry powder/silica gel=1/30 with silica gel; W/w), glass tube column 3.2 * 48.5cm, mobile phase toluene (Toluene): ethyl acetate (Ethyl; Acetate; EA) volume ratio=7: 3, stream is washed 15 times of colloid gap bed volumes (Bed volume=250ml), i.e. 3750ml altogether.Eluat is divided into several according to predeterminated target partly to be collected.Each partly is evaporated to dried, and then with small amount of methanol Hui Rong, gather candy gel (Sephadex LH-20) and further separates (dry powder/gel=1/100 Portugal of reinjecting; W/w); Glass tube column 1.5 * 40cm is a mobile phase with methanol, and stream is washed 1 times of colloid gap bed volume (Bed volume=30m1) altogether; Be 30ml, can get the separating medium of P2-1, B2-2, P3-1 and P3-2.Each separating medium is evaporated to dried, and carries out purification with preparation HPLC respectively, obtain chemical compound (P3-1=46mg accounts for the 2.3 weight % of EX-1) and the P3-2 chemical compound (73mg) (accounting for the 3.65 weight % of EX-1) of P2-1, P2-2, P3-1.
Get six depositions after centrifugal with methanol Hui Rong, be evaporated to dried.Separate so that silica gel (Silica Gel 60) is further (dry powder/silica gel=1/30, w/w), glass tube column 3.2 * 48.5cm, mobile phase toluene: ethyl acetate=9: 1, stream is washed 2 times of colloid gap bed volumes (Bed volume=250ml), i.e. 500ml altogether.Eluat is divided into several according to predeterminated target partly to be collected.Each partly is evaporated to dried, and then with small amount of methanol Hui Rong, gather candy gel (Sephadex LH-20) and further separates (dry powder/gel=1/100 Portugal of reinjecting; W/w); Glass tube column 1.5 * 40cm is a mobile phase with methanol, and stream is washed 1 times of colloid gap bed volume (Bed volume=30ml) altogether; Be 30ml, can get the chemical compound of P3-3 and P3-4.
Structure is identified
The ESI-MS of P2-1 shows its [M+Na]
+(+mode) is m/z 603.3, [M-H]
-Be m/z 579.2.The NMR data of P2-1 is measured.Knowing its molecular formula by inference by above-mentioned data is C
34H
28O
9With aforesaid data and document Fukai, T.; Hano, Y; Hirakura, K.; Nomura, T.; Uzawa, J.; Fukushima, K.,
Structure of mulberrofuran J, a2-arylbenzofuran derivative from the cultivated Mulberry tree (Morus lhou Koidz.), Heterocycles 1984,22, and 1007-1011 compares, and confirms that P2-1 is mulberrofuran C.This chemical compound was also once isolated (JP57-144223) from the root bark of mulberry.
The ESI-MS of P2-2 shows its [M+Na]
+(+mode) is m/z 715.3, [M-H]
-Be m/z 691.3.The NMR data of P2-2 is measured.Knowing its molecular formula by inference by above-mentioned data is C
40H
36O
11With aforesaid data and document Nomura, T.; Fukai, T.; Narita, T.,
Hypotensive constituent, kuwanon H, a New flavone derivative from the root bark of the cultivated mulberry tree (Morus Alba L.), Heterocycles 1980,14, and 1943-1951. compares, and proves that its structure is albanin F (kuwanon G).This chemical compound was also once isolated (KR20020087225) from Cortex Mori.
The ESI-MS of P3-1 shows its [M+H]
+(+mode) is m/z 695.4, [M-H]
-Be m/z 693.7.The NMR data of P3-1 is measured.Knowing its molecular formula by inference by above-mentioned data is C
40H
38O
11With aforesaid data and document Fukai, T.; Hano, Y; Fujimoto, T.; Nomura, T.,
Structure of sanggenon G, A new Diels-Alder adduct from the Chinese crude drug " Sang-Bai-Pi " (Morus root Barks), Heterocycles 1983,20, and 611-615 compares, and confirms that its structure is sanggenon G.This chemical compound was also once isolated (JP10-007555) from Cortex Mori.
P3-2 records [M+H] respectively through ESI-MS
+, [M+Na]
+And [M-H]
-Be m/z 761,783 and 759, push away to such an extent that its molecular weight is 760 thus.The NMR data of P3-2 is measured.Knowing its molecular formula by inference by above-mentioned data is C
45H
44O
11Warp is compared with following three pieces of documents, confirms that P3-2 is kuwanon H (that is albanin A or moracenin A) [Nomura, T.; Fukai, T.; Narita, T.; Terada, S.; Uzawa, J.; Iitaka, Y; Takasugi, M.; Ishikawa, S.I.; Nagao, S.; Masamune, T.,
Confirmation of The structures of kuwanons G and H (albanins F and G) by partial synthesis, Tetrahedron Letters 1981,22,2195-2198; Oshima, Y; Konno, C.; Hikino, H.,
Structure of moracenin A, a hypotensive principle of Morus root barks, Heterocycles 1980,14,1287-1290; Oshima, Y; Konno, C.; Hikino, H.; Matsushita, K.,
Structure of moracenin B, a hypotensive principle of Morus root barks, Tetrahedron Letters 1980,21,3381-3384].JP56-123979 discloses this chemical compound has hypotensive activity.
The ESI-MS of P3-3 shows its [M+H]
+Be m/z 421.The NMR data of P3-3 is measured.Knowing its molecular formula by inference by above-mentioned data is C
25H
24O
6Warp and document Nomura, T.; Fukai, T.; Yamada, S.; Katayanagi, M.,
Phenolic constituents of the cultivated mulberry tree (Morus alba L.), Chem.Pharm.Bull.1976,24,2898-2900 compares, and confirmation P3-3 is morusin.This chemical compound once was used to treat oral disease (CN101148443A and CN101148451A) by report.
The ESI-MS of P3-4 shows its [M+H]
+Be m/z 447.0.The NMR data of P3-4 is measured.Knowing its molecular formula by inference by above-mentioned data is C
29H
34O
4With document Nomura, t; Fukai, T.; Shimada, T.; Chen, I.-S.Mulberrofuran D,
A new 2-arylbenzofuran from the root barks of the Mulberrytree (Morus australis Poir.), Heterocycles, 1982,19,1855-1860 compares, and confirms that P3-4 is mulberrofuran D.This chemical compound once was used to treat oral disease (JP10-007555) by report.
The pharmacologically active experiment
Staphylococcus aureus (Staphylococcus aureus (Smith)), and anti-methicillin staphylococcus aureus (Staphylococcus aureus Methicillin Resistant) (ATCC 33591), external germ experiment.
Tester is to add fixed [the Edwards J.R.et al.In vitro antibacterial activity of SM-7338 of prediction by the bouillon media dilution method to the minimal inhibitory concentration (MIC) of staphylococcus aureus; Acarbapenem antibiotic with stability to dehydropeptidase I.Antimicrobial AgentsChemotherapy.33:pp.215-222,1989].Tester be dissolved in mass concentration be 100% dimethyl sulfoxine (dimethyl sulfoxide, DMSO) and sequence diluted.Experiment is carried out with 48 hole culture plates.Tester solution with 0.01ml during test makes an addition to 48 hole culture plates, adds the 1-5x10 that contains of 0.99ml again
5The Mueller-Hinton nutritional solution of the staphylococcus aureus of CFU/ml or anti-methicillin staphylococcus aureus (ATCC 33591) (DIFCO, USA).The first water concentration of DMSO is 1% in the culture fluid.The maximum concentration of tester then is 100 μ g/ml.Culture plate was cultivated 20 hours in 37 ℃, and subsequently with macroscopy, growth or the turbidity scoring that suppresses staphylococcus aureus is just (+), suppress to grow up or the turbidity scoring for bearing (-).Solvent and active reference material are then respectively as blank and positive control.Each test is all carried out with two multiple modes.The result is shown in table 1.
Streptococcus pneumoniae (Streptococcus pneumoniae) (ATCC 6301); And anti-erythromycin and Ampicillin streptococcus pneumoniae (Streptococcus pneumoniae (Erythromycin and Ampicillin Res.Clin.Isol.)), external germ experiment.
Tester is to add fixed [the Edwards J.R.et al.In vitro antibacterial activity of SM-7338 of prediction by the bouillon media dilution method to the minimal inhibitory concentration (MIC) of streptococcus pneumoniae; A carbapenemantibiotic with stability to dehydropeptidase I.Antimicrobial Agents Chemotherapy.33:pp.215-222,1989].Tester be dissolved in mass concentration be 100% dimethyl sulfoxine (dimethylsulfoxide, DMSO) and sequence diluted.Experiment is carried out with 48 hole culture plates.Tester solution with 0.01ml during test makes an addition to 48 hole culture plates, and the mass concentration that contains that adds 0.99ml again is 7% fetal bovine serum and 1-5x10
5The Tryptic Soy nutritional solution of the streptococcus pneumoniae of CFU/ml (ATCC 6301) or anti-erythromycin and Ampicillin streptococcus pneumoniae (clinical segregator) (DIFCO, USA).The first water concentration of DMSO is 1% in the culture fluid.The maximum concentration of tester then is 1001 μ g/ml.Culture plate was cultivated 20 hours in 37 ℃, and subsequently with macroscopy, growth or the turbidity scoring that suppresses streptococcus pneumoniae is just (+), suppress to grow up or the turbidity scoring for bearing (-).Solvent and active reference material are then respectively as blank and positive control.Each test is all carried out with two multiple modes.The result is shown in table 1.
The antibacterial action of table 1 extract EX-1 and unification compound wherein
MIC: minimal inhibitory concentration
SA (Smith): staphylococcus aureus;
MRSA: anti-methicillin staphylococcus aureus
SP: streptococcus pneumoniae
SP (EM & AM Res.): anti-erythromycin and Ampicillin streptococcus pneumoniae
Can find out that from the data of above table 1 the P3-2 chemical compound all has very effective inhibitory action to the growth of staphylococcus aureus (SA) and anti-methicillin staphylococcus aureus (MRSA), especially both MIC are 0.3 identical μ g/ml.Compared to gentamycin, its MIC value to MRSA is 10 times to the MIC value of SA.
The P3-1 chemical compound also all presents effective inhibitory action to the growth of staphylococcus aureus (SA) and anti-methicillin staphylococcus aureus (MRSA) in addition, and its MIC value is respectively 1 and 3 μ g/ml.The P3-1 chemical compound also all presents effective inhibitory action to the growth of streptococcus pneumoniae (SP) and anti-erythromycin and Ampicillin streptococcus pneumoniae (SP (EM&AMRes.)), and its MIC value is respectively 30 and 10 μ g/ml.
Make us unexpected, extract EX-1 of the present invention all has very effective inhibitory action to the growth of staphylococcus aureus (SA) and anti-methicillin staphylococcus aureus (MRSA), and both MIC are respectively 0.3 and 1 μ g/ml.Because EX-1 only contains the P3-2 chemical compound of 3.65 weight % and the P3-1 chemical compound of 2.3 weight %.Multiple composition contained in the very possible extract EX-1 of the present invention produces the effect that multiplies each other, and so low MIC value could be arranged the growth of staphylococcus aureus (SA) and anti-methicillin staphylococcus aureus (MRSA).
Claims (13)
1. purposes for preparing the medicine that can treat bacterial infection with the Kuwanon H or its pharmaceutical acceptable salt of tool formula (I) structure:
2. purposes as claimed in claim 1, wherein this antibacterial is a gram positive bacteria.
3. purposes as claimed in claim 2, wherein this antibacterial is a staphylococcus aureus.
4. purposes as claimed in claim 3, wherein this antibacterial is anti-methicillin staphylococcus aureus.
5. purposes as claimed in claim 2, wherein this antibacterial is a streptococcus pneumoniae.
6. purposes as claimed in claim 5, wherein this antibacterial is anti-erythromycin and Ampicillin streptococcus pneumoniae.
7. the extract with little Radix et Cortex Mori prepares the purposes of the medicine of treating bacterial infection; Wherein the extract of this little Radix et Cortex Mori comprises formula (I) structural compounds of 1-5% and formula (II) chemical compound of 1-5%; Weight with this extract is benchmark, and the extract of this little Radix et Cortex Mori is produced via the method that comprises the following step:
A) with this little Radix et Cortex Mori of 95 weight % ethanol waters extraction;
B) concentration step extract a);
C) concentrate with step b) imports a reverse-phase chromatography pipe and washes this tubing string with first-class washing liquid and second flowing lotion stream in regular turn; With the eluat that obtains first-class washing liquid and the eluat of second flowing lotion; Wherein this first-class washing liquid is 50 weight % ethanol waters, and this second flowing lotion is 95 weight % ethanol waters; And
D) collect the eluat of this second flowing lotion, and volatilization removes solvent wherein.
8. purposes as claimed in claim 7, wherein the extract of this little Radix et Cortex Mori comprises 3.7% formula (I) structural compounds and 2.3% formula (II) chemical compound, is benchmark with the weight of the extract of this little Radix et Cortex Mori.
9. purposes as claimed in claim 7, wherein this antibacterial is a gram positive bacteria.
10. purposes as claimed in claim 9, wherein this antibacterial is a staphylococcus aureus.
11. purposes as claimed in claim 10, wherein this antibacterial is anti-methicillin staphylococcus aureus.
12. purposes as claimed in claim 9, wherein this antibacterial is a streptococcus pneumoniae.
13. purposes as claimed in claim 12, wherein this antibacterial is anti-erythromycin and Ampicillin streptococcus pneumoniae.
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Citations (1)
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| CN1562171A (en) * | 2004-03-22 | 2005-01-12 | 沈阳药科大学 | Medicinal preparation of having antivirus function and preparation method |
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| CN1562171A (en) * | 2004-03-22 | 2005-01-12 | 沈阳药科大学 | Medicinal preparation of having antivirus function and preparation method |
Non-Patent Citations (2)
| Title |
|---|
| Ya-Qin Shi,et al..Phenolic Constituents of the Root Bark of Chinese Morus australis.《Natural Medicines》.2001,第55卷(第3期),第143-146页. * |
| 戴胜军.桑属植物中Diels-Alder型加成物的结构、光谱特征及生理作用.《药学学报》.2005,第40卷(第10期),第876-881页. * |
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