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WO2019227969A1 - Antibiotique de type polycétide à cycle complet d'atomes de carbone d'ansamycine et ses usages dans la préparation de médications antimicrobiennes ou de médications antitumorales - Google Patents

Antibiotique de type polycétide à cycle complet d'atomes de carbone d'ansamycine et ses usages dans la préparation de médications antimicrobiennes ou de médications antitumorales Download PDF

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Publication number
WO2019227969A1
WO2019227969A1 PCT/CN2019/075053 CN2019075053W WO2019227969A1 WO 2019227969 A1 WO2019227969 A1 WO 2019227969A1 CN 2019075053 W CN2019075053 W CN 2019075053W WO 2019227969 A1 WO2019227969 A1 WO 2019227969A1
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kendomycin
verrucosispora
scsio
human
extract
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Chinese (zh)
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鞠建华
孙长利
张善文
桂春
张华�
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South China Sea Institute of Oceanology of CAS
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South China Sea Institute of Oceanology of CAS
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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
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/18—Bridged systems
    • 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
    • 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
    • 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
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • 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

Definitions

  • the invention belongs to the technical field of microorganisms, and particularly relates to a marine wart spore (Verrucosispora sp.) SCSIO07399 and three kinds of new kendomycin compounds kendomycin BD extracted and isolated from the strain.
  • the invention also relates to the preparation of the three new compounds by the strain Methods and applications.
  • Kendomycin is a polyketone compound of the ansamycin antibiotic family.
  • the mother nucleus is characterized by a macrolide mixed with a quinone methyl chromophore. It was originally isolated from Streptomyces AL-71389 by Takeda Pharmaceutical Company as an antagonist of the endothelin receptor in 1996. [Bruck KB, Rychnovsky SD. Formal synthesis of (-)-kendomycin featuring aprins-cyclization method to construct the macrocycle [J] .J Am Chem Soc, 2008.130 (39): 13177-13181]. In 1998, Su et al.
  • Bode and Zeeck determined their absolute configuration through the Mosher reaction [Bode, H, B, Zeeck, A. Structure, and biosynthesis of Kendomycin, a carbocyclic, ansa-compound, from Streptomyces [J]. 58 (3): 323-328].
  • kendomycin antibiotics have good biological activity, not only a wide range of antibacterial spectrum, but also inhibit methicillin-resistant Staphylococcus aureus and vancomycin-resistant Staphylococcus aureus, and also have a significant number of human tumor cells. Toxic activity, and is expected to develop into endocortin receptor antagonists and anti-osteoporosis agents [Magauer T, Martin HJ, Mulzer J. Ring-closing metathesis and photo-fries reaction for the construction of the ansamycin antibioticskendomycin: development a protecting group free oxidation endgame [J] .Chemistry, 2010,16 (2): 507-519].
  • One of the objectives of the present invention is to provide a marine wart spore (Verrucosispora sp.) SCSIO 07399 capable of producing kendomycin BD, which was deposited at the Guangdong Provincial Center for Microbial Strains (GDMCC) on October 22, 2018, address : 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, Guangdong Provincial Institute of Microbiology, Deposit No .: GDMCC No. 60466.
  • Another object of the present invention is to provide an ansa full carbocyclic polyketide antibiotic kendomycin B-D as shown in formulae (I), (II) and (III), or a pharmaceutically acceptable salt thereof:
  • formula (I) is kendomycin B
  • formula (II) is kendomycin C
  • formula (III) is kendomycin D.
  • the third object of the present invention is to provide the application of marine wart spore (Verrucosispora sp.) SCSIO 07399 in the preparation of kendomycin B-D.
  • the fourth object of the present invention is to provide a method for preparing kendomycins B-D.
  • the kendomycin B-D is prepared from a fermented culture of Verrucosispora sp. SCSIO 07399.
  • kendomycin B-D is prepared from a fermented culture of Verrucosispora sp. SCSIO07399, and specifically includes the following steps:
  • the fraction Fr.B5 is passed through a Sephex LH-20 glucan gel chromatography column, and the volume ratio of CHCl 3 / MeOH is 1: 1. The phases were eluted, and the fractions were collected and purified to obtain kendomycin D.
  • Fr.B7 was passed through a Sephex LH-20 glucan gel column and eluted with CHCl 3 / MeOH volume ratio 1: 1 as the mobile phase. The fractions were collected. After further purification, kendomycin B and kendomycin C were obtained.
  • Verrucosispora sp. SCSIO 07399 is inserted into a seed medium, and a seed culture liquid is obtained by fermentation.
  • the seed culture liquid is connected to a fermentation medium, and a fermentation culture is obtained by fermentation.
  • the formula of the seed medium For: 10g of soluble starch, 4g of yeast extract, 2g of bacteriological peptone and 30g of sea salt per liter, the balance is water; the formula of the fermentation medium is: 20g of soluble starch, 10g of glucose, 10g of maltose, 5g of corn flour per liter , 10g of malt extract powder, 2g of CaCO 3 and 30g of sea salt, the balance is water.
  • a sixth object of the present invention is to provide an antibacterial or antineoplastic drug, which contains an effective amount of the kendomycin B, kendomycin C or kendomycin D, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the antibacterial drug is a drug against Bacillus thuringiensis, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, or methicillin-resistant Staphylococcus aureus;
  • the antitumor drug is anti-human gastric cancer, human lung cancer , Human cervical cancer, human liver cancer, human breast adenocarcinoma, or human colorectal cancer.
  • the present invention provides a strain of marine wart spore (Verrucosispora sp.) SCSIO 07399 capable of producing kendomycin antibiotics.
  • a new compound kendomycin BD can be prepared by using this bacterium. These three compounds have significant antibacterial and antitumor activities and have broad Application prospects.
  • the Verrucosispora sp. SCSIO07399 of the present invention was deposited on October 22, 2018 at the Guangdong Provincial Center for Microbial Strains (GDMCC), Address: 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, Guangdong Institute of Microbiology, deposit number: GDMCC No. 60466.
  • Fig. 1 is a morphological diagram of Verrucosispora sp. SCSIO 07399 on M-ISP4 medium;
  • Figure 2 is a phylogenetic tree of Verrucosispora sp. SCSIO 07399, where 07399 represents Verrucosis pora sp. SCSIO 07399;
  • Figure 3 is an HPLC chart of the production of kendomycin B and kendomycin C by SCSIO 07399 from Verrucosispora sp .;
  • Example 1 Isolation and identification of Verrucosispora sp. SCSIO 07399
  • the Verrucosispora sp. SCSIO 07399 of the present invention is isolated from a sediment sample in the South China Sea.
  • the colonies are small, usually orange-yellow, slender mycelium, branched, and not broken. Basal hyphae were formed, and occasionally sparse slightly white aerial hyphae (as shown in Figure 1).
  • Extract the genomic DNA of the isolated strain PCR-amplify its 16SrDNA sequence (the nucleotide sequence is shown in SEQ ID NO.1) by conventional methods, and perform sequencing analysis to construct a phylogenetic tree based on the 16SrDNA sequence (such as Figure 2) shows that the sequence similarity between strain SCSIO 07399 and Verrucosispora sp. R8-37 16SrDNA is 99%, indicating that strain SCSIO 07399 belongs to Verrucosispora sp.
  • the identified strain SCSIO 07399 belongs to a species of the genus Warthospora, named Verrucosispora sp. SCSIO 07399, which was deposited in the Guangdong Provincial Center for Microbial Strains on October 22, 2018. (GDMCC), Address: 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, Guangdong Provincial Institute of Microbiology, Deposit No .: GDMCC No. 60466.
  • seed medium Each liter of seed medium contains 10g of soluble starch, 4g of yeast extract, 2g of bacteriological peptone, and 30g of sea salt, and the balance is water. The above components are mixed uniformly and the pH is adjusted to 7.0. Prepare 1L seed medium, and then aliquot it into 20 250mL Erlenmeyer flasks, each 50mL, and sterilize at 121 ° C for 30min.
  • Each liter of fermentation medium contains 20g of soluble starch, 10g of glucose, 10g of maltose, 5g of corn flour, 10g of malt extract powder, 2g of CaCO 3 and 30g of sea salt. The balance is water. Mix well and adjust pH to 7.0. Prepare 1L fermentation medium, then aliquot it into 5 1L Erlenmeyer flasks and sterilize at 121 ° C for 30min for later use.
  • the fermented culture of Verrucosispora sp. SCSIO 07399 was centrifuged (3800 ⁇ 4000r / min, 10 ⁇ 15min) to separate the fermentation supernatant from the mycelium; the fermentation supernatant was treated with methyl ethyl ketone, etc. Extraction was performed three times in volume. The methyl ethyl ketone phase was condensed by rotary evaporation to obtain extract A. The mycelium was immersed and extracted with acetone (2L), and the acetone extract was obtained by ultrasonic treatment. Cream B.
  • Extract A and extract B are similar. Extract A and extract B are combined, and subjected to normal phase silica gel column chromatography, using chloroform-methanol as the mobile phase. Different volume ratios (100: 0, 99 : 1, 98: 2, 96: 4, 94: 6, 92: 8, 9: 1, 8: 2, 5: 5, 0: 100), followed by gradient elution, and eluted under a gradient of 100% chloroform.
  • the fraction was recorded as Fr.A1
  • the fraction eluted under a gradient of chloroform-methanol volume ratio of 99: 1 was recorded as Fr.A2
  • the fraction eluted under a gradient of chloroform-methanol volume ratio of 98: 2 was recorded as Fr.A3.
  • Fr.A4 The fraction eluted under a gradient of chloroform-methanol volume ratio of 96: 4 is recorded as Fr.A4, and the fraction eluted under a gradient of chloroform-methanol volume ratio of 94: 6 is recorded as Fr.A5.
  • the fraction eluted under a gradient of 92: 8 was recorded as Fr.A6, the fraction eluted under a gradient of 9: 1 was recorded as Fr.A7, and the volume ratio of chloroform-methanol was determined under a gradient of 8: 2.
  • Compound 1 is a yellow powder with molecular formula C 28 H 40 O 6 , HR-ESI-MS m / z 471.2757 ([MH] - ); [ ⁇ ] 20 D -59 (c 0.21, MeOH); UV (MeOH) ⁇ max (log ⁇ ) 202 (4.276), 307 (3.681) nm; IR (film): v max : 3325, 2937, 2358, 2341, 1602, 1456, 1359, 1195, 1095, 1022 cm -1 .
  • H-12 and C-14 can be observed in the HMBC spectrum; H-13 and C-14, C-15, C-24; H-15 and C-13, C-14, C-24; H-16 Correlation with C-14 and H-24 with C-13, C-14, C-15, it is inferred that the above two fragments are connected through C-14.
  • 8 typical aromatic carbons in compound 1 are shown: ⁇ C 173.9 (C-1), 96.7 (C-2), 183.9 (C-3), 148.2 (C-4) 113.0 (C-4a), 120.6 (C-19), 143.5 (C-20) and 131.4 (C-20a) are a polysubstituted pyranone ring structure.
  • Compound 3 is a yellow powder with molecular formula C 33 H 47 NO 9 S, HR-ESI-MS m / z 471.2757 ([MH] - ); [ ⁇ ] 20 D -240 (c 0.34, MeOH); UV (MeOH) ⁇ max (log ⁇ ) 202 (4.328), 244 (3.591), 382 (3.453) nm; IR (film): v max : 3363, 2949, 2362, 2330, 1602, 1373, 1010 cm -1 . By nuclear magnetic spectrum assignment, it was determined that compound 3 and 1 contained the same 22-membered polysubstituted pyranolactone ring as the mother core structure.
  • H-27 ( ⁇ H 3.52, ⁇ H 3.87) and C-20 ( ⁇ C 151.5) and C-28 ( ⁇ C 55.1H-28 ( ⁇ H 4.60) and C-27 ( ⁇ C 35.8) C-29 ( ⁇ C 173.9) and C-30 ( ⁇ C 172.7), H-31 ( ⁇ H 1.93) and C-30 ( ⁇ C 172.7) are remotely correlated, and combine 1 H- 1 H
  • the coupling of H-27 ( ⁇ C 35.8) and H-28 ( ⁇ H 4.60) in COSY infers the existence of acetylacetylcysteine.
  • the filter paper sheet method was used to test the antibacterial activity of the compound, and it was found that compounds 1-3 had certain antibacterial activity against most Gram-positive bacteria.
  • Bacillus thuringiensis BT01 Bacillus subtilis BS01, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 292292, Staphyureococcus 745a And methicillin-resistant Staphylococcus aureus shhs-A1
  • 96-well plate method was used to determine the minimum inhibitory concentration, kanamycin, ampicillin and vancomycin were used as positive controls.
  • the minimum inhibitory concentration (MIC) of compound 1 against Staphylococcus aureus ATCC 29213, Staphylococcus aureus 745524, Enterococcus faecalis ATCC 29212, and Bacillus thuringiensis BT01 were 0.5, 1.0, 2.0, 1.0 ⁇ g / mL, respectively, which were better than those of card.
  • the minimum inhibitory concentration (MIC) of Bacillus BT01 was 0.5, 1.0, 1.0, 0.5, 0.5 ⁇ g / mL, which was better than the positive controls of kanamycin, ampicillin, and vancomycin.
  • Compounds 1-3 were applied to human gastric cancer cell line MGC803 (human gastric cancer cell line), human lung cancer cell line A549 (human lung cancer cell line) and human cervical cancer cell line Hela (human cervical cancer cell line) by standard MTT method.
  • Six human cancer cell lines including the human hepatocellular carcinoma cell line HepG2, the human breast adenocarcinoma cell line MCF-7, and the colorectal carcinoma cell line RKO Human liver cell line L02 (normal human human hepatic cell line) and human umbilical vein endothelial cell line Huvec-12 (normal human human vein endothelial cell line) were tested for cytotoxic activity, and cisplatin was used as a positive control.

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Abstract

L'invention concerne un antibiotique de type polycétide à cycle complet d'atomes de carbone d'ansamycine et ses usages dans la préparation de médicaments antimicrobiens ou de médicaments antitumoraux. Elle concerne Verrucosispora sp. SCSIO 07399 conservée le 22 octobre 2018 au centre de collecte de cultures microbiennes du Guangdong (GDMCC) dont l'adresse est : Guangdong Institute of Microbiology, 100 Xianlie Middle Road, Building 59, 5ᵗʰ floor, Guangzhou, et dont le numéro de conservation est GDMCC No. 60466. La culture de fermentation de Verrucosispora sp. SCSIO 07399 peut produire de nouveaux composés de kendomycines B à D, comme l'indiquent les formules (I) à (III). Lesdits trois composés ont des activités antimicrobiennes et antitumorales notables.
PCT/CN2019/075053 2019-01-28 2019-02-14 Antibiotique de type polycétide à cycle complet d'atomes de carbone d'ansamycine et ses usages dans la préparation de médications antimicrobiennes ou de médications antitumorales Ceased WO2019227969A1 (fr)

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CN201910081520.2A CN109810919B (zh) 2019-01-28 2019-01-28 一类安莎全碳环聚酮类抗生素及其在制备抗菌药物或抗肿瘤药物中的应用

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CN114525216B (zh) * 2021-11-15 2024-01-05 塔里木大学 一种游动放线菌靶向分离方法
CN114605430B (zh) * 2022-03-18 2023-09-05 中国科学院海洋研究所 一种大环双内酯类化合物及其制备方法和应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101921721A (zh) * 2010-08-02 2010-12-22 福建省微生物研究所 一种新的海洋疣孢菌菌株及其应用
CN103319496A (zh) * 2012-03-23 2013-09-25 中国科学院微生物研究所 来源于海洋疣孢菌的多环聚酮类化合物及其制备方法与应用
CN105287498A (zh) * 2015-11-16 2016-02-03 淄博齐鼎立专利信息咨询有限公司 Kendomycin C在制备抗血小板聚集药物中的应用
CN105326826A (zh) * 2015-11-15 2016-02-17 淄博齐鼎立专利信息咨询有限公司 Kendomycin B在制备抗抑郁药物中的应用

Family Cites Families (1)

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Publication number Priority date Publication date Assignee Title
CN105287491A (zh) * 2015-11-09 2016-02-03 淄博齐鼎立专利信息咨询有限公司 Kendomycin A在制备治疗促进小肠蠕动药物中的应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101921721A (zh) * 2010-08-02 2010-12-22 福建省微生物研究所 一种新的海洋疣孢菌菌株及其应用
CN103319496A (zh) * 2012-03-23 2013-09-25 中国科学院微生物研究所 来源于海洋疣孢菌的多环聚酮类化合物及其制备方法与应用
CN105326826A (zh) * 2015-11-15 2016-02-17 淄博齐鼎立专利信息咨询有限公司 Kendomycin B在制备抗抑郁药物中的应用
CN105287498A (zh) * 2015-11-16 2016-02-03 淄博齐鼎立专利信息咨询有限公司 Kendomycin C在制备抗血小板聚集药物中的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHANG, SHANWEN: "Studies on antibiotics products of three marine-derived actinomycetes", 31 December 2018 (2018-12-31) *

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