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WO2006059400A1 - Antibiotiques fki-2140, procédé de fabrication de ces antibiotiques et souche produisant ces antibiotiques - Google Patents

Antibiotiques fki-2140, procédé de fabrication de ces antibiotiques et souche produisant ces antibiotiques Download PDF

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Publication number
WO2006059400A1
WO2006059400A1 PCT/JP2004/018443 JP2004018443W WO2006059400A1 WO 2006059400 A1 WO2006059400 A1 WO 2006059400A1 JP 2004018443 W JP2004018443 W JP 2004018443W WO 2006059400 A1 WO2006059400 A1 WO 2006059400A1
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Prior art keywords
substance
antibiotic
fki
absorption spectrum
producing
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Ceased
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English (en)
Japanese (ja)
Inventor
Hiroshi Tomoda
Rokuro Masuma
Satoshi Omura
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Kitasato Institute
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Kitasato Institute
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Anticipated expiration legal-status Critical
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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
    • C12P17/10—Nitrogen as only ring hetero atom
    • C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
    • 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
    • C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings

Definitions

  • the present invention relates to an antibiotic FK 1-2140 useful as an animal drug, agricultural chemical or pharmaceutical product having growth inhibitory activity against, for example, microorganisms, nematodes and arthropods, a method for producing the same, and a strain.
  • the antibiotic FK 1 -2 1 40 is FK I-1 40 A 1 or A 2 substance (stereoisomer of FK I-2 140 A1 substance; hereinafter referred to as A 1 substance stereoisomer), and / Or FK 1 -2140 B substance, and Z or FK I-2 1 40 C substance, and / or FK 1 -2 1 40 D substance, and or FK 1 -21 40 E substance, and Z or FK 1 -2 1 40 F substance and Z or FK I-2 1 40 G 1 or G 2 substance (stereoisomer of FK I 2 1 40 G 1 substance; hereinafter referred to as G 1 stereoisomer) is there.
  • antibiotics produced by microorganisms have been discovered so far. Among them, some antibiotics such as penicillin, streptomycin, amphotericin B, Thai mouth shin, monensin, ivernuctin, blasticidin S, polyoxin have been put to practical use in the fields of pharmaceuticals, veterinary drugs and agricultural chemicals. It is also well known that mitomycin (, bleomycin, doxorubicin, aclarubicin, adriamycin, etc. are put to practical use as anticancer agents in the pharmaceutical field (Yoshio Ueno, Satoshi Omura, “Microbial Drug Chemistry, Revised”). 3rd edition, "1 79-245, Nanedo, 1 995).
  • An object of the present invention is an antibiotic FK useful as a veterinary or agrochemical, pharmaceutical product having growth inhibitory activity against microorganisms, nematodes, arthropods, etc. that can solve various problems such as toxicity, side effects and tolerance. It provides 1-2140, its production method and strains.
  • the present inventors have continued to search for metabolites produced by microorganisms, and as a result, microorganisms, nematodes, and so on in the culture of FK1-2140 strain newly isolated from soil. It was found that substances having growth inhibitory activity against arthropods were produced. Subsequently, the active substance was separated and purified from the culture, and as a result, the following formula [I or]!
  • Antibiotic FK I-2140 G 1 or G 2 (stereoisomer of G 1), and these substances are collectively called antibiotic FK I-2140.
  • FK 1 -2140 B substance represented by: and / or the following formula [IV]]
  • FK 1 -2140 C substance represented by: and / or the following formula [V]
  • FK 1 -2140 D substance represented by: and / or the following formula [VI]
  • An antibiotic FK 1 -2140 comprising FK 1 -2 140 G 1 or G 2 substance (stereoisomer of G 1 substance) represented by the formula:
  • the present invention further includes formulas [I] to [! X] FK I— 21 4 OA 1 or A 2 substance (stereoisomer of A 1 substance), and / or FK 1-2 1 40 B substance, and Z or FK 1 -21 40 C substance , And Pino or FK 1 -2 1 40 D substance, and Z or FK 1 -21 40 E substance, and ⁇ or FK 1 -2140 F substance, and or FK I-21 40 0 1 or 0 2 substance (G
  • the present invention provides an antibiotic FK 1-21 40 exhibiting growth inhibitory activity against arthropods, which comprises one stereoisomer) as an active ingredient.
  • the present invention further belongs to a filamentous fungus and has the formulas [I] to [!
  • FK I-21 40 A1 or A 2 substance (stereoisomer of A 1 substance), and / or FK 1 -2 1 40 B substance, and or FK 1 -21 40 C3 ⁇ 4 quality, and / or FK 1—21 40 D substance, and Z or FK 1 -2 1 40 E substance, and Z or FK I—2 1 40 F substance, and or FK I—2 1 40 G 1 or G 2 (G 1 substance
  • Microorganisms capable of producing (stereoisomers) are cultured in a medium, and FK I-21 40A1 or A2 substance, and / or FK1-21 40B substance, and / or FK I-21 40 are contained in the culture.
  • Substance C and / or FK 1-21 40 D Substance and / or FK 1 -21 40 E Substance and Z or FK 1 -21 40 F Substance and / or FK I-21 40 G 1 or G 2 Accumulate substances from the culture, FK I-21 40A 1 or A2 substance, and / or FK 1-21-240 B substance, and or FK 1-21 40 C substance, and Z or FK I-21 21 D Substance, and Z or FK 1 -2 1 40 E substance, and Z or FK 1 -21 40 F substance, and or FK I -2 1 40 G 1 or G 2 substances are collected.
  • the production method of antibiotic FK 1 -2 1 40 is provided.
  • the present invention further relates to a microorganism belonging to a filamentous fungus and capable of producing the antibiotic FK 1-21 40, Penicillium sp. (Penici 1 1 i urn s p.) FKI-21 40 (FERM ABP-1 0 1 65) or a variant thereof, which provides a method for producing the antibiotic FK 1-2140.
  • the present invention further relates to Penicillum sp. FK I—2 140 (FERM ABP— 1 0 1) which belongs to filamentous fungi and has the ability to produce the antibiotic FK 1-21 40. 65).
  • the bacteriological properties of the FK1-2140 strain of the present invention are as follows.
  • This strain grew well on lapec yeast extract agar medium, 25% glycerin, nitrate agar medium, wort agar medium, Miura agar medium, etc., and conidia were well established on various agar mediums.
  • Penicillus is formed at the tip of the conidia pattern.
  • Penicillus is a single wheeler, composed of 3 to 10 phialides.
  • the phialide was an ampoule type with a size of 8 to 12 X 2.0 to 3.5 / m.
  • Fia mouth-type conidia are formed from the tip of the phialide and become chained as the culture time elapses.
  • the conidia are spherical to subspherical, grayish green in size, 2.8 to 3.0 X 2. 7 to 3.0 m, and have a streaky surface.
  • Table 1 Medium Growth condition on medium Colony surface Colony back surface Color of soluble pigment (co-alpha diameter) Wapek Yeast extract agar medium
  • the optimal growth conditions for this strain are pH 3-7 and temperature 16.8-8-32.3 ° C.
  • the growth range of this strain is pH 2-8, temperature 1 1.5-5-3 5. 6 ° C.
  • this strain belongs to the genus Penicillium (Penici 1 1 i urn). It was identified as one strain belonging to it and named Benicillium 'SP FK I—2 1 4 0. This strain is named Penicillium 'SP FK I-21 40 (Penici 1 1 i urn s p. FK I-21 40) and is based on the Budapest Treaty on the International Approval of Deposit of Microorganisms in Patent Procedures.
  • Preferred examples of the FK 1-21 40 substance-producing bacterium used in the present invention include the aforementioned Penicillium sp. (Penici 1 1 iurn s p.) FK I-2 140 strain.
  • fungi are generally susceptible to mutations in mycological characteristics and are not constant, and are naturally or commonly used UV irradiation or mutant derivatives such as N-methyl-N'-nitro- It is a well-known fact that mutations are caused by artificial mutation means using N-nitrosoguanidine, ethyl methanesulfonate, etc., and such artificial mutants as well as natural mutants belong to filamentous fungi.
  • Formula [I] ⁇ [! Any strain having the ability to produce the antibiotic FK 1 -2 1 40 represented by X] can be used in the present invention.
  • an antibiotic FK1-21-240-producing bacterium belonging to the filamentous fungus is cultured in a medium and separated from the culture. Separation. Performed by purification.
  • Nutrient sources suitable for production of the antibiotic FK 1-2140 of the present invention may be those that can be used as a nutrient source for filamentous fungi.
  • peptone for example, commercially available peptone, meat extract, corn's steeple liquor, cottonseed powder, peanut powder, soy flour, yeast extract, NZ—amine, casein hydrate, soda nitrate, ammonium nitrate, ammonium sulfate Nitrogen sources such as glycerin, starch, glucose, galactose, mannose, etc., or carbon sources such as fat, and inorganic salts such as salt, phosphate, calcium carbonate, magnesium sulfate, etc. alone or in combination Can be used.
  • Nitrogen sources such as glycerin, starch, glucose, galactose, mannose, etc.
  • carbon sources such as fat
  • inorganic salts such as salt, phosphate, calcium carbonate, magnesium sulfate, etc. alone or in combination Can be used.
  • metal salts and animal oils, vegetable oils and mineral oils can be added as antifoaming agents as necessary. Any of these may be used as long as they are useful for the production of the antibiotic FK I-2 140 using the producing bacteria, and all known filamentous fungal culture materials can be used. Liquid culture and stationary culture are preferred for mass culture of antibiotic FK I-21 40, and the culture temperature can be applied within the range in which the producing bacteria can grow and antibiotic FK 1-2140 can be produced. Culturing can be carried out by appropriately selecting according to the properties of the antibiotic FK I-2 140 substance producing bacteria using the conditions described above.
  • Antibiotic FK I-2 140 can be extracted from the culture medium with a water-immiscible organic solvent such as chloroform or ethyl acetate.
  • a water-immiscible organic solvent such as chloroform or ethyl acetate.
  • known methods used for collecting fat-soluble substances such as adsorption chromatography, gel filtration chromatography, scraping from thin layer chromatography, centrifugal countercurrent distribution chromatography, high performance liquid chromatography It can be collected purely by appropriately combining or repeating the first class.
  • Infrared absorption spectrum Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 2. imax 3426, 29 1 0, 1 683, 1 606, 1 508, 1 247, 1 027, 759 cm 1 showing characteristic absorption maxima,
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in black mouth form, ethyl acetate, acetone, methanol and acetonitrile. Insoluble in water and n-hexane.
  • UV absorption spectrum UV absorption spectrum measured in ethanol Is as shown in Fig. 3; imax 208, 226, and 250 nm, showing special absorption maxima.
  • Red external absorption spectrum Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 4; imax 3253, 2925, 1 702, 1 608, 1 502, 1 253 , 1 033, shows a Japanese ⁇ absorption maximum at 8 1 1 cm 1,
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in chloroform, ethyl acetate, acetone, methanol, and acetonitrile. Insoluble in water, n-hexane,
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in black mouth form, ethyl acetate, acetone, methanol and acetonitrile. Insoluble in water, n-hexane,
  • UV absorption spectrum The ultraviolet absorption spectrum measured in ethanol is as shown in Fig. 7, showing characteristic absorption maxima near imax 220, 279, and 324 nm.
  • Infrared absorption spectrum Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 8, imax 3268, 2964, 1 689, 1 608, 1 509, 1 378, 1 257, 1 08 1, 1 033, 806 cm 1 showing characteristic absorption maxima,
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in black mouth form, ethyl acetate, acetone, methanol, and acetonitrile. Insoluble in water, n-hexane,
  • Red external absorption spectrum Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 10, imax 3428, 2937, 1 687, 1 6 1 0, 1 5 1 1 378, 1 257, 1 072, 825, 67 l cm 1 showing characteristic absorption maxima,
  • Solubility in solvents Soluble in black mouth form, ethyl acetate, acetone, methanol, and acetonitrile. Insoluble in water, n-hexane, (9) Color reaction: Brown with sulfuric acid.
  • Infrared absorption spectrum Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 12. imax 2937, 1 687, 1 600, 1 25
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in black mouth form, ethyl acetate, acetone, methanol and acetonitrile. Insoluble in water, n-hexane, (9) Color reaction: Brown with sulfuric acid.
  • Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 14, imax 3426, 2925, 1 689, 1 60 8, 1 46 1, 1 26 1, 1 093, 1 03 1, 806 cm—showing a special absorption maximum at 1 ,
  • Solubility in solvents Soluble in formaldehyde, ethyl acetate, acetone, methanol, and acetonitrile. Insoluble in water, n-hexane,
  • UV absorption spectrum measured in ethanol is as shown in Fig. 15; absorption characteristic around imax 218, 284, 295, 326 nm Showing maximum,
  • Red external absorption spectrum Infrared absorption spectrum measured by KBr tablet method is as shown in Fig. 16; imax 3421, 2962, 2857, 1700, 1604, 1 26 1, 1 0 97, 1 033, 806 cm—shows characteristic absorption maxima in 1 ,
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in chloroform, ethyl acetate, acetone, methanol and acetonitrile. Insoluble in water, n-hexane,
  • Infrared absorption spectrum measured by the KBr tablet method is as shown in Fig. 18. ⁇ & ⁇ 3409, 2925, 2859, 1 69 7, 1 604, 1 259 , 1 shows the 099, 1 035, 806 cm JP ⁇ absorption electrode size to 1,
  • s is a single line
  • d is a double line
  • t is a triple line
  • q is a quadruple line
  • Solubility in solvents Soluble in black mouth form, ethyl acetate, acetone, methanol, and acetonitrile. Insoluble in water, n-hexane,
  • FK I—21 40 A 1 substance, FK I—21 40 A 2 substance, FK 1 -21 40 B substance, FK I—2 1 40 C substance, FK I—21 40 D substance, FK 1 ⁇ 2 1 40 E substance, FK I— 21 40 F substance, FK I-2 1 40 G 1 substance and FK 1— 2 1 40 G 2 substance have been described in detail for various physicochemical properties. No compound has been reported so far and the antibiotic FK 1 -21 4 0 was determined to be a novel substance.
  • the antibiotic FK I — 2140 of the present invention exhibits growth inhibitory activity against arthropods, such as insecticides. Can be used as a medicine.
  • Arthropods are generic names for organisms that have nodes in their bodies and that cover and protect the body with a substance called chitin, and include organisms such as centipedes, ticks, spiders, rikiji and shrimp.
  • FIG. 1 is an ultraviolet absorption spectrum of the FK 1 -21 40 A 1 substance of the present invention.
  • FIG. 2 is an infrared absorption spectrum of the FK I 1 2 140 A 1 substance of the present invention.
  • FIG. 3 is an ultraviolet absorption spectrum of the FK I-2 1 40 A 2 substance of the present invention.
  • FIG. 4 is an infrared absorption spectrum of the FK I 2 1 4 OA 2 substance of the present invention.
  • FIG. 5 is an ultraviolet absorption spectrum of the FK I-2 1 40 0 B substance of the present invention.
  • FIG. 6 is an infrared absorption spectrum of the FK I 1 2 1 4 0 B substance of the present invention.
  • FIG. 7 is an ultraviolet absorption spectrum of the FK I-2 1 40 C material of the present invention.
  • FIG. 8 shows the infrared absorption spectrum of the FK I-2 140 C material of the present invention.
  • FIG. 9 is an ultraviolet absorption spectrum of the FK I 2 1 4 0 D substance of the present invention.
  • FIG. 10 shows the infrared absorption spectrum of the FK I-2 140D material of the present invention.
  • Fig. 11 shows the ultraviolet absorption spectrum of the FK I-2 1 40 E substance of the present invention.
  • Fig. 12 shows the infrared absorption spectrum of the FK I-2 1 40 E substance of the present invention.
  • Figure 13 shows the UV absorption spectrum of the FK I-2 1 40 F substance of the present invention.
  • Fig. 14 shows the infrared absorption spectrum of FK I-2 1 40 F substance of the present invention.
  • Figure 15 shows the ultraviolet absorption spectrum of the FK I ⁇ 2 1 40 G 1 substance of the present invention.
  • Fig. 6 shows the infrared absorption spectrum of the FK I-2 1 40 G 1 substance of the present invention.
  • Fig. 7 shows the ultraviolet absorption spectrum of the FK I ⁇ 2 1 40 G 2 substance of the present invention.
  • Fig. 8 shows the infrared absorption spectrum of the FK I ⁇ 2 1 40 G 2 substance
  • Benicillium sp. FK I—2 1 40 strain (FE RM A BP— 1 0 1 65) cultured on agar slant medium, glucose 2.0%, polypeptone (Nippon Pharmaceutical Co., Ltd., Japan) 0.5%, Yeast extract (Oriental Yeast Co., Ltd., Japan) 0.2%, agar 0.1%, potassium dihydrogen phosphate 0.1%, magnesium sulfate heptahydrate 0.05% liquid medium (pH 5.7)
  • a platinum loop was inoculated into a 500 ml 1-volume Erlenmeyer flask containing 100 ml of 1) and cultured with shaking at 27 ° C for 3 days.
  • Seed culture it As a liquid, Glucose 1.0%, Soluble starch 2.0%, Soybean oil 2.0%, Pharmamedia (Iwaki, Japan) 1.0%, Meat extract (Kyokuto Pharmaceutical, Japan) ) 60 ml of 500 ml triangular flasks containing 100 ml of liquid medium consisting of 0.5%, calcium carbonate 0.3%, magnesium sulfate heptahydrate 0.1%, agar 0.1% 1 ml each was inoculated and cultured with shaking at 27 ° C for 3 days. This was transferred in 20 Oml portions into 30 1 L roux flasks and incubated at 27 ° C for 1 day.
  • FK I-21 40 Crude substance I was subjected to high performance liquid chromatography (CAP CELL PAK C 1 8. 020 X 25 Omm, Shiseido, Japan), and 50% acetonitrile was used as the mobile phase to separate the peaks. By concentration under reduced pressure, 4.9 mg of FK I—21 40 C substance, 9.8 mg of FKI—21 40 D substance, 2.2 mg of FK I—21 40 E substance, 4.8 mg of FKI—21 40 F substance could be isolated, and 97.5 mg of FK I—2 1 40A1 substance, FK I—2 1 4 OA 2 substance, and FK I—21 40 B substance were obtained.
  • microorganisms belonging to filamentous fungi and capable of producing antibiotic FK 1-21 40 are cultured in a medium, and antibiotic FK I-2 140 substance is accumulated in the culture, and the culture is performed.
  • Antibiotic FK I-2140 collected from foods is useful as an animal medicine or pesticide because it has growth inhibitory activity against arthropods, and is expected to be effective as a medicine.

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Abstract

La présente invention décrit un microorganisme (Penicillium sp. FKI-2140, FERM ABP-10165), qui appartient à la famille des champignons et qui est capable de produire les antibiotiques FKI-2140 (FKI-2140A1 ou A2, et/ou FKI-2140B, et/ou FKI-2140C, et/ou FKI-2140D, et/ou FKI-2140E, et/ou FKI-2140F, et/ou FKI-2140G1 ou G2), cultivé dans un milieu pour accumuler de cette façon les antibiotiques FKI-2140 dans le milieu de culture. Ensuite, les antibiotiques FKI-2140 sont recueillis à partir du milieu de culture. Du fait qu’elles ont un effet d’inhibition de la croissance sur les arthropodes, on prévoit que les substances obtenues pourront être utilisées en tant que médicaments destinés aux animaux, pesticides et médicaments.
PCT/JP2004/018443 2004-12-03 2004-12-03 Antibiotiques fki-2140, procédé de fabrication de ces antibiotiques et souche produisant ces antibiotiques Ceased WO2006059400A1 (fr)

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Cited By (8)

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WO2010128095A1 (fr) * 2009-05-07 2010-11-11 Novartis Ag Compositions ectoparasiticides
CN104886063A (zh) * 2015-06-15 2015-09-09 牛赡光 化合物Yaequinolone B的应用
WO2017036128A1 (fr) * 2015-09-06 2017-03-09 中国海洋大学 Composé alcaloïde, son procédé de préparation et son utilisation en tant qu'agent antiviral contre le virus herpès simplex de type 1
CN106554307A (zh) * 2015-09-29 2017-04-05 于跃 一种海洋真菌来源的抗病毒喹啉酮生物碱类衍生物的制备方法
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WO2009060015A1 (fr) 2007-11-09 2009-05-14 Novartis Ag Nouvelle utilisation
JP2011503029A (ja) * 2007-11-09 2011-01-27 ノバルティス アーゲー 殺外部寄生虫薬としてのジヒドロキノリノン
AU2008324224B2 (en) * 2007-11-09 2013-12-05 Elanco Tiergesundheit Ag Dihydroquinolinones as ectoparasiticides
US8648091B2 (en) 2007-11-09 2014-02-11 Novartis Ag Dihydroquinolinones as ectoparasiticides
WO2010128095A1 (fr) * 2009-05-07 2010-11-11 Novartis Ag Compositions ectoparasiticides
EP2248422A1 (fr) 2009-05-08 2010-11-10 Novartis AG Compositions pour lutter contre les ectoparasites
CN104886063A (zh) * 2015-06-15 2015-09-09 牛赡光 化合物Yaequinolone B的应用
WO2017036128A1 (fr) * 2015-09-06 2017-03-09 中国海洋大学 Composé alcaloïde, son procédé de préparation et son utilisation en tant qu'agent antiviral contre le virus herpès simplex de type 1
US10639303B2 (en) 2015-09-06 2020-05-05 Ocean University Of China Alkaloids and their preparation and application as anti-HSV-1 agents
CN106554307A (zh) * 2015-09-29 2017-04-05 于跃 一种海洋真菌来源的抗病毒喹啉酮生物碱类衍生物的制备方法
CN106554307B (zh) * 2015-09-29 2019-09-27 扬州蓝色生物医药科技有限公司 一种海洋真菌来源的抗病毒喹啉酮生物碱类衍生物的制备方法
CN109776550A (zh) * 2019-01-17 2019-05-21 广东轻工职业技术学院 一种海洋真菌来源的新型生物碱化合物及其在制备食品防腐剂中的应用
CN109810055A (zh) * 2019-01-17 2019-05-28 广东轻工职业技术学院 一种海洋真菌来源的新型生物碱化合物及其在制备抗肺癌药物中的应用
CN109776550B (zh) * 2019-01-17 2021-08-10 广东轻工职业技术学院 一种海洋真菌来源的生物碱化合物及其在制备食品防腐剂中的应用

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