WO2015030197A1 - 抗真菌活性を有する新規微生物産物 - Google Patents
抗真菌活性を有する新規微生物産物 Download PDFInfo
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- WO2015030197A1 WO2015030197A1 PCT/JP2014/072796 JP2014072796W WO2015030197A1 WO 2015030197 A1 WO2015030197 A1 WO 2015030197A1 JP 2014072796 W JP2014072796 W JP 2014072796W WO 2015030197 A1 WO2015030197 A1 WO 2015030197A1
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- compound
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- pharmaceutically acceptable
- acceptable salt
- antifungal
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- IPQNWQFGNBVBSM-XNJYKOPJSA-N C/C=C(\Cc1ccccc1)/C1(C2)ON1CCC2O Chemical compound C/C=C(\Cc1ccccc1)/C1(C2)ON1CCC2O IPQNWQFGNBVBSM-XNJYKOPJSA-N 0.000 description 2
- IPQNWQFGNBVBSM-SILLCRNTSA-N C/C=C(/Cc1ccccc1)\C1(C2)ON1CCC2O Chemical compound C/C=C(/Cc1ccccc1)\C1(C2)ON1CCC2O IPQNWQFGNBVBSM-SILLCRNTSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
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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
- C12P17/14—Nitrogen or oxygen as hetero atom and at least one other diverse hetero ring atom in the same ring
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/465—Streptomyces
Definitions
- the present invention relates to a compound having a novel mother nucleus, its use as an antifungal agent, its production method and the like.
- the present invention has been made in view of the above-described present situation in the technical field, and provides a compound having a novel mother nucleus that can be a promising drug seed compound, its use as an antifungal agent, a production method thereof, and the like.
- the task is to do.
- the present inventors have focused on marine microbial resources in view of the above-described current situation in search for novel drug candidate compounds. Marine microbial resources are rarely used so far and have great potential for the discovery of new secondary metabolites. However, a special technique is required for collecting the separation source, and the culture technique is not well established. The present inventors diligently studied a method for collecting samples from the ocean, a method for culturing and evaluating microorganisms, and succeeded in isolating promising microbial strains for the development of antifungal agents. According to 16S ribosomal nucleotide sequence analysis, the microorganism strain was found to be Streptomyces actinomycetes.
- a medicament or agrochemical comprising the compound according to [1] or [2] above or a pharmaceutically acceptable salt thereof.
- the medicament or pesticide according to the above [4] which targets a fungus of a genus selected from the group consisting of Candida and Aspergillus.
- [6] A method for producing a compound according to [1] or [2] above or a pharmaceutically acceptable salt thereof, which is a Streptomyces bacterium represented by accession number NITE BP-01677 or a variant thereof Culturing in a medium containing a carbon source to produce the compound or a pharmaceutically acceptable salt thereof in the medium, and recovering the compound or a pharmaceutically acceptable salt thereof from the culture. Including said method.
- [7] A Streptomyces bacterium represented by accession number NITE BP-01677 or a mutant thereof.
- the present invention also provides the following.
- Mycosis in a mammal comprising administering an effective amount of the compound according to [1] or [2] above or a pharmaceutically acceptable salt thereof to the mammal in need thereof.
- Prevention or treatment method [9] A method for controlling plant diseases, which comprises treating the target crop and / or seeds of the target crop with an effective amount of the compound according to [1] or [2] or a pharmaceutically acceptable salt thereof.
- the compound according to the above [1] or [2] or a pharmaceutically acceptable salt thereof for use in preventing or treating mycosis in a mammal.
- the compound of the present invention is useful as an antifungal agent because of its low molecular weight, low reactivity with serum, and strong antifungal activity. Further, the compound of the present invention has a new mother nucleus and is promising as a seed compound for developing a new drug. The present invention also provides a process for producing the compounds of the present invention.
- KKRM represents the compound of the present invention
- MCFG represents Micafungin
- AMPH represents amphotericin B
- 5-FC represents flucytosine
- FLCZ represents fluconazole
- ITCZ represents itraconazole
- VRCZ represents voriconazole
- MCZ represents miconazole.
- the present invention has the following formula:
- the compound of the present invention may include one or more isomers such as an optical isomer based on an asymmetric carbon atom and a geometric isomer based on a double bond, but all of these isomers and mixtures thereof are included. It is included in the scope of the present invention.
- the wavy line adjacent to the double bond portion is intended to include both of the following two types of geometric isomers.
- Examples of pharmaceutically acceptable salts include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, or acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, and the like. And salts with organic acids such as acid, succinic acid, methanesulfonic acid and p-toluenesulfonic acid.
- inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, or acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, and the like.
- organic acids such as acid, succinic acid, methanesulfonic acid and p-toluenesulfonic acid.
- the compound of the present invention can be produced by using the Streptomyces bacterium (hereinafter also referred to as the bacterium of the present invention) isolated from sea sand of Kakeijima, Kagoshima Prefecture, or a mutant thereof. it can.
- the bacterium is deposited at 2-5-8, Kazusa Kamashichi, Kisarazu City, Chiba Prefecture, at the Patent Microorganism Depositary, Center for Product Evaluation Technology (Accession number: NITE P-1677, Deposit date: August 1, 2013) ), NITE P-01677 made a transfer request to deposit under the Budapest Treaty, and the request was received on July 30, 2014 (transfer date), and has been deposited internationally under the accession number: NITE BP-01677.
- the color of the aerial hyphae is gray, and the spore chain shows a short helical form. Soluble pigments produce yellowish pigments. The color of the back surface shows a light yellowish color from cream. Aged spores form a spore mass.
- the mutant is not particularly limited as long as it is a strain derived from the bacterium of the present invention and can produce the compound of the present invention.
- the mutant may have the same nucleotide sequence of the 16S rRNA gene as the nucleotide sequence of the 16S rRNA gene of the bacterium of the present invention (ie, 100% match) or substantially the same (eg, as described below). Such as when produced by mutagenesis in the presence of mutagenic substances).
- the mutant also exhibits morphological and physiological characteristics similar to those of the bacterium of the present invention.
- nucleotide sequence “substantially identical to the nucleotide sequence of the 16S rRNA gene of the bacterium of the present invention” is a nucleotide sequence to be compared of at least 99% or more, preferably 99.1%. As mentioned above, it means having nucleotide sequence identity of 99.2% or more, more preferably about 99.5% or more.
- the mutant can be produced, for example, by modifying the bacterium of the present invention.
- modification treatment include mutation in the presence of a mutagenic substance, etc., and introduction of a gene that can enhance the usefulness of the bacterium of the present invention (for example, a gene that increases the ability to produce the compound of the present invention). And disruption of genes possessed by the bacterium of the present invention, and combinations of these manipulations.
- the bacterium of the present invention or a mutant thereof can be maintained and propagated by culturing in a nutrient medium containing a carbon source.
- the carbon source include saccharides (eg, monosaccharides such as glucose and galactose, disaccharides such as sucrose, polysaccharides such as starch), glycerin, and the like, preferably starch.
- the nutrient medium preferably also contains a nitrogen source, and examples of the nitrogen source include kajiton, yeast extract, meat extract, malt extract and the like.
- the early production of the compound of the present invention can be promoted by adding NaH 2 PO 4 to the medium.
- the concentration thereof is usually about 10% -40% of the seawater concentration (ie, artificial seawater 38.4 g / L).
- the artificial seawater concentration of the medium is, for example, 0.384 g / L to 38.4 g / L, preferably 1.92 g / L to 13.04 g / L, and more preferably 3.84 g / L to 15.36 g / L.
- the salt content include sodium chloride, magnesium chloride, magnesium sulfate, calcium sulfate, and potassium chloride.
- composition of an exemplary media, starch 4%, 0.4% meat extract, casitone 0.4%, a NaH 2 PO 4 0.1% yield also be a 10% liquid medium usually seawater concentration.
- Other culture conditions include agitation culture at pH 6.8 to 7.5 (eg 7.0) and 25 to 35 ° C. (eg 28 ° C.).
- the compound of the present invention can be produced in a culture by culturing the bacterium of the present invention or a mutant thereof, for example, for 2 to 14 days under the culture conditions as described above. From the culture, the compound of the present invention can be recovered, preferably isolated and purified. Isolation and purification can be performed using methods well known in the art, and for example, means such as concentration, extraction, chromatography, reprecipitation, recrystallization and the like can be used.
- the compound of the present invention has strong antifungal activity against a wide range of fungi, as shown in the Examples below. Therefore, the compound of the present invention is useful as an antifungal agent, for example. Therefore, the present invention also provides an antifungal agent (also referred to as the antifungal agent of the present invention) containing the compound of the present invention as an active ingredient.
- the antifungal agent of the present invention can be used as a medicine or as an agricultural chemical.
- Examples of the fungi targeted by the antifungal agent of the present invention include Candida albicans ( Candida albicans , Candida parapsilosis , Candida tropicalis , Candida krusei , Candida glabrata , Candida quilliermondii , Candida lusitaniae, etc.), Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus , etc.), Trichophyton (eg: Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum, including but fungus Trichophyton verrucosum, etc.), and the like.
- the mycosis is not particularly limited, and examples thereof include deep dermatomycosis, deep mycosis, mycoma, or mycoemia.
- the target crop in the case of using the antifungal agent of the present invention as an agrochemical is not particularly limited, and examples thereof include cereals (eg, rice, barley, wheat, rye, oats, corn, potato, etc.), beans (soybeans) , Red beans, broad beans, peas, peanuts, etc.), fruit trees and fruits (apples, citrus fruits, pears, grapes, peaches, plums, cherry peaches, walnuts, almonds, bananas, strawberries, etc.), vegetables (cabbage, tomatoes, spinach) , Broccoli, lettuce, onion, leek, green pepper, etc.), root vegetables (carrots, potatoes, sweet potatoes, radish, lotus root, turnips, etc.), crops for processing (cotton, hemp, kouzo, mitsumata, rapeseed, beet, hops, sugar cane , Sugar beet, olive, rubber, coffee, tobacco, tea, etc.), moss (pumpkin, cucumber, watermelon
- the agrochemical can be used in the following forms, and is usually used together with adjuvants commonly used in the pharmaceutical field.
- the compounds of the present invention can be obtained by known methods, for example, emulsion stock solution, sprayable paste, sprayable or dilutable solution, diluted emulsion, wettable powder, water solvent, powder, granule, flowable, dry flowable, smoke Formulated into capsules, fumigants, and capsules, eg with polymeric substances.
- Additives and carriers when solid preparations are intended, vegetable powders such as soybean flour, wheat flour, mineral fine powders such as diatomaceous earth, apatite, gypsum, talc, bentonite, clay, sodium benzoate, urea, Organic and inorganic compounds such as mirabilite are used.
- liquid dosage forms vegetable oils, mineral oils, aromatic hydrocarbons such as kerosene, xylene and toluene, amides such as formamide, dimethylformamide, sulfoxides such as dimethyl sulfoxide, methyl isobutyl ketone Further, ketones such as acetone, trichloroethylene, water and the like are used as a solvent.
- a surfactant may be added if necessary to take a uniform and stable form.
- the wettable powder, emulsion, aqueous solution, flowable agent, and dry flowable agent thus obtained are diluted with water to a predetermined concentration to form a suspension or emulsion, and the powder and granules are left as is in the soil or plant. Used in a spraying method.
- the content and application rate of the active ingredient in the agricultural chemical containing the compound of the present invention can be varied widely depending on the dosage form, the type of fungus to be applied, the target crop and the like.
- the antifungal agent of the present invention when used as a medicine, it is orally administered to a treatment target, for example, a mammal (eg, human, mouse, rat, hamster, rabbit, cat, dog, cow, sheep, monkey, etc.). Alternatively, it can be administered by any parenteral route (for example, intravenous injection, intramuscular injection, subcutaneous administration, rectal administration, or transdermal administration).
- a mammal eg, human, mouse, rat, hamster, rabbit, cat, dog, cow, sheep, monkey, etc.
- parenteral route for example, intravenous injection, intramuscular injection, subcutaneous administration, rectal administration, or transdermal administration.
- an oily base an emulsifier and an emulsion stabilizer, a solubilizer, a powder component, a polymer component, a tackiness improver, and a film forming agent
- PH adjuster antioxidant, preservative, preservative, shape-retaining agent, moisturizer, skin protectant, cooling agent, fragrance, colorant, chelating agent, lubricant, blood circulation promoter, astringent, tissue repair
- An accelerator, an antiperspirant, a plant extract component, an animal extract component, an anti-inflammatory agent, an antipruritic agent and the like can be blended as necessary. Any of these additives that are generally used in pharmaceutical preparations can be used.
- the antifungal agent of the present invention is a cream, solution, lotion, emulsion, tincture, ointment, aqueous gel, oily gel, by the above-mentioned components other than the active ingredients, etc., commonly used in the pharmaceutical preparation field. It can be formulated and used as an external preparation such as an aerosol, powder, shampoo, soap, or enamel for nail application.
- the antifungal agent of the present invention When administered orally, it can be prepared in a dosage form suitable for oral administration such as capsules, tablets, granules, powders, pills, fine granules, troches and the like. These preparations are excipients, bulking agents, binders, wetting agents, disintegrating agents, surfactants, lubricants, dispersants, buffering agents, preservatives, dissolution agents commonly used for oral preparations. It can be produced by conventional methods using additives such as adjuvants, preservatives, flavoring agents, soothing agents and stabilizers.
- Example 1 Isolation and analysis of Streptomyces sp.
- Strain A84 A separation source was collected from sea sand in Kakeroma Island, Kagoshima Prefecture. Strains were isolated from the collected samples, and the isolated microorganism strains were subjected to evaluation screening using antifungal activity as an index. As a result, a promising strain was obtained, which was further examined. The strain was subjected to 16S rRNA phylogenetic analysis, and the producing bacteria were Streptomyces genus actinomycetes, and related species were Streptomyces nodosus (98.8% homology) and Streptomyces glomeratus (99.0% homology). )Met.
- Streptomyces sp. A84 strain Streptomyces sp. A84 strain was deposited at 2-5-8, Kazusa Kamashichi, Kisarazu City, Chiba Prefecture, to the Patent Microorganism Depositary, National Institute of Technology and Evaluation (Accession Number: P-01677, Date of Deposit: August 1, 2013) NITE P-01677 made a request for transfer from NITE P-01677 to a deposit under the Budapest Treaty, and the request was received on July 30, 2014 (transfer date), and was deposited internationally under the accession number: NITE BP-01677 .
- Example 2 Examination of production medium of A84 strain The production medium of A84 strain was examined. As a result of the examination of the medium, the following medium showed good productivity.
- Medium composition Starch 4% Kaziton 0.1% NaH 2 PO 4 0.1% Artificial seawater (Marine Art Super Formula 1, manufactured by Tomita Pharmaceutical) 0.384% pH 7.0 As culture conditions, 100 ml of medium was placed in a 300 ml Erlenmeyer flask and cultured at 28 ° C., 200 rpm for 2-4 days.
- Example 3 Separation, purification and analysis of active ingredient
- the strain A84 was inoculated into a 300 ml Erlenmeyer flask containing 100 ml of the medium having the composition described in Example 2, and cultured at 28 ° C and 200 rpm (rotary shaker) for 3 days.
- the culture solution was subjected to solvent extraction using an equal amount of ethyl acetate, and then ethyl acetate was concentrated.
- the dried sample was dissolved in a small amount of methanol, and purified by column chromatography separation by HPLC using an ODS column (95% purity or more, 100 ⁇ g / 1 L).
- LC / MS analysis, NMR analysis, and optical rotation measurement of the active ingredient were performed.
- the measurement conditions are as follows.
- Magnet SCM 14.o1T Bore diameter: 54mm
- Probe 3mm, 5mm, 10mm
- Measuring solvent Deuterated methanol rotation: Polarimeter: P-1030 (manufactured by JASCO)
- Solvent Methanol (for HPLC)
- the molecular formula was determined to be C 15 H 19 NO 2
- the molecular weight was determined to be 245.1416, and the NMR spectrum was determined as shown in FIG.
- the specific optical rotation was -3.25000 deg
- Experimental Example 1 Measurement of antifungal activity The minimum growth inhibitory concentration (MIC) was measured by a micro liquid dilution method. The measurement was performed using a yeast-like fungus FP “Eiken” (Eiken Chemical Co., Ltd.) according to the instructions of the product.
- MIC minimum growth inhibitory concentration
- Fig. 2 shows the MIC ( ⁇ g / mL) for each bacterial species of various drugs.
- the active ingredient of the present invention showed good activity against Candida spp. And Aspergillus spp.
- the compound of the present invention is useful as an antifungal agent because of its low molecular weight, low reactivity with serum, and strong antifungal activity. Further, the compound of the present invention has a new mother nucleus and is promising as a seed compound for developing a new drug. The present invention also provides a process for producing the compounds of the present invention.
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Abstract
Description
[1]下記式:
[2]重メタノールを測定溶媒として測定される13C-NMRおよび1H-NMRのスペクトルが下記:
[3]上記[1]または[2]に記載の化合物またはその薬学的に許容される塩を含有してなる医薬または農薬。
[4]抗真菌薬である、上記[3]に記載の医薬または農薬。
[5]カンジダ属およびアスペルギルス属からなる群から選択される属の真菌を標的とするものである、上記[4]に記載の医薬または農薬。
[6]上記[1]または[2]に記載の化合物またはその薬学的に許容される塩の製造方法であって、受託番号NITE BP-01677で表されるストレプトマイセス属細菌またはその変異体を、炭素源を含有する培地で培養して該化合物またはその薬学的に許容される塩を培地中に産生させ、該培養物から該化合物またはその薬学的に許容される塩を回収することを含む、前記方法。
[7]受託番号NITE BP-01677で表されるストレプトマイセス属細菌またはその変異体。
[8]上記[1]または[2]に記載の化合物またはその薬学的に許容される塩の有効量を、それを必要とする哺乳動物に投与することを含む、該哺乳動物における真菌症の予防または治療方法。
[9]上記[1]または[2]に記載の化合物またはその薬学的に許容される塩の有効量を対象作物および/または対象作物の種子に処理することを含む、植物病害の防除方法。
[10]哺乳動物における真菌症の予防または治療に使用するための上記[1]または[2]に記載の化合物またはその薬学的に許容される塩。
鹿児島県加計呂麻島の海砂から分離源を採集した。採集した試料から菌株を単離し、単離した微生物株を抗真菌活性を指標とした評価スクリーニングに供した。その結果、有望な菌株が得られたので、それを更に精査した。
該菌株を16S rRNAの系統分類法による解析に供したところ、生産菌はストレプトマイセス属の放線菌であり、近縁種としてはStreptomyces nodosus(98.8%相同性)およびStreptomyces glomeratus(99.0%相同性)であった。最も近縁であるStreptomyces glomeratusとの塩基配列の相同性は99.0%であったため、新種の可能性が示唆された。本菌株をStreptomyces sp. A84株と命名した。Streptomyces sp. A84株を千葉県木更津市かずさ鎌足2-5-8、独立行政法人製品評価技術基盤機構特許微生物寄託センターに寄託し(受託番号:P-01677,寄託日:2013年8月1日)、NITE P-01677からブタペスト条約に基づく寄託への移管請求を行い、当該請求が2014年7月30日(移管日)に受領され、受託番号:NITE BP-01677で国際寄託されている。
A84株の生産培地について検討した。
培地検討の結果、下記の培地において良好な生産性を示した。
培地組成:
スターチ 4%
カジトン 0.1%
NaH2PO4 0.1%
人工海水(マリンアート スーパーフォーミュラ1、富田製薬製)
0.384%
pH 7.0
培養条件として300ml容三角フラスコに培地100mlを入れ28℃、200rpm、2-4日培養した。
A84株を実施例2に記載の組成の培地100mlを入れた300ml容三角フラスコに接種し、28℃、200rpm(ロータリーシェーカー)で3日間培養した。培養液を等量の酢酸エチルを用いて溶媒抽出した後、酢酸エチルを濃縮した。乾燥試料を少量のメタノールに溶解し、ODSカラムを用いたHPLCでカラムクロマト分離を実施し精製を行った(95%純度以上、100μg/1L)。
装置:型番Agilent6540
イオン源:AJS-ESI、ESI、APC1
NMR:
装置:ECA-600(日本電子製)
マグネット:SCM 14.o1T
ボア径:54mm
プローブ:3mm、5mm、10mm
測定溶媒:重メタノール
旋光度:
旋光度計:P-1030(日本分光製)
溶媒:メタノール(HPLC用)
試料濃度:4mg/ml
温度:28
セル:3.5mmX10.0mmφ、円筒型硝子セル(mod.CG3-10)
λ:589nm
その結果、分子式はC15H19NO2、分子量は245.1416と決定され、NMRスペクトルは図1に示される通りに決定された。また、比旋光度は-3.25000 deg(Avg)、旋光度は-0.0013 deg(Avg)であった。
微量液体希釈法により最少発育阻止濃度(MIC)を測定した。測定は、酵母様真菌FP'栄研'(栄研化学株式会社)を用い、製品の説明書に従って行った。
Claims (7)
- 請求項1または2に記載の化合物またはその薬学的に許容される塩を含有してなる医薬または農薬。
- 抗真菌薬である、請求項3に記載の医薬または農薬。
- カンジダ属およびアスペルギルス属からなる群から選択される属の真菌を標的とするものである、請求項4に記載の医薬または農薬。
- 請求項1または2に記載の化合物またはその薬学的に許容される塩の製造方法であって、受託番号NITE BP-01677で表されるストレプトマイセス属細菌またはその変異体を、炭素源を含有する培地で培養して該化合物またはその薬学的に許容される塩を培地中に産生させ、該培養物から該化合物またはその薬学的に許容される塩を回収することを含む、前記方法。
- 受託番号NITE BP-01677で表されるストレプトマイセス属細菌またはその変異体。
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CA2922452A CA2922452A1 (en) | 2013-08-29 | 2014-08-29 | Novel microbial product having antifungal activity |
ES14840178.9T ES2655049T3 (es) | 2013-08-29 | 2014-08-29 | Nuevo producto microbiano que tiene actividad antifúngica |
US14/915,106 US9896457B2 (en) | 2013-08-29 | 2014-08-29 | Microbial product having antifungal activity |
JP2015534344A JP6620931B2 (ja) | 2013-08-29 | 2014-08-29 | 抗真菌活性を有する新規微生物産物 |
EP14840178.9A EP3040338B1 (en) | 2013-08-29 | 2014-08-29 | Novel microbial product having antifungal activity |
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EP3243825A1 (en) | 2016-05-11 | 2017-11-15 | Seed Research Institut Co., Ltd. | Oxaziridine compound and production method thereof |
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- 2014-08-29 CA CA2922452A patent/CA2922452A1/en not_active Abandoned
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Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2016136963A1 (ja) * | 2015-02-27 | 2016-09-01 | 彰彦 石川 | カケロマイシンおよびその誘導体の製造方法 |
JPWO2016136963A1 (ja) * | 2015-02-27 | 2017-12-21 | オーピーバイオファクトリー株式会社 | カケロマイシンおよびその誘導体の製造方法 |
US20190023667A1 (en) * | 2015-02-27 | 2019-01-24 | Op Bio Factory Co., Ltd. | Method for producing kakeromycin and derivatives thereof |
JP2019194214A (ja) * | 2015-02-27 | 2019-11-07 | オーピーバイオファクトリー株式会社 | カケロマイシンおよびその誘導体の製造方法 |
US10618876B2 (en) * | 2015-02-27 | 2020-04-14 | Op Bio Factory Co., Ltd. | Method for producing kakeromycin and derivatives thereof |
CN114874131A (zh) * | 2015-02-27 | 2022-08-09 | 海洋规划生物工厂株式会社 | Kakeromycin及其衍生物的制造方法 |
US11753385B2 (en) | 2015-02-27 | 2023-09-12 | Op Bio Factory Co., Ltd. | Method for producing kakeromycin and derivatives thereof |
EP3243825A1 (en) | 2016-05-11 | 2017-11-15 | Seed Research Institut Co., Ltd. | Oxaziridine compound and production method thereof |
CN107365321A (zh) * | 2016-05-11 | 2017-11-21 | 株式会社种探索研究所 | 氧杂氮杂环丙烷化合物及其制备方法 |
JP2017206492A (ja) * | 2016-05-11 | 2017-11-24 | 株式会社シード探索研究所 | オキサアジリジン化合物およびその製造方法 |
CN107365321B (zh) * | 2016-05-11 | 2021-06-29 | 株式会社种探索研究所 | 氧杂氮杂环丙烷化合物及其制备方法 |
Also Published As
Publication number | Publication date |
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ES2655049T3 (es) | 2018-02-16 |
US20160207937A1 (en) | 2016-07-21 |
EP3040338A4 (en) | 2017-01-04 |
CA2922452A1 (en) | 2015-03-05 |
CN105960408B (zh) | 2018-02-23 |
EP3040338A1 (en) | 2016-07-06 |
CN105960408A (zh) | 2016-09-21 |
US9896457B2 (en) | 2018-02-20 |
JPWO2015030197A1 (ja) | 2017-03-02 |
JP6620931B2 (ja) | 2019-12-18 |
EP3040338B1 (en) | 2017-10-11 |
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