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Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by Pseudophialophora sp. BF-0158

The Journal of Antibiotics volume 73, pages 211–223 (2020)Cite this article

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Abstract

Eight new potentiators of antifungal amphotericin B (AmB) activity, phialotides A to H, were isolated from the fermentation broths of the rare fungus Pseudophialophora sp. BF-0158. The structures of phialotides were elucidated by spectroscopic analyses, including NMR and MS, and degradation studies. Phialotides were novel polyketide glycosides consisting of a 1,3-dimethylbut-1-ene (C6-unit) repeating substructure and one to three hexopyranoses. None of the phialotides exhibited antifungal activity, whereas all potentiated AmB activity against several fungi. Phialotide F was the most effective potentiator of AmB activity against Candida albicans, with a decrease in the MIC from 0.50 to 0.016 µg ml−1 being observed in combination with phialotide F at 1.0 µg ml−1.

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References

  1. Trejo WH, Bennett RE. Streptomyces nodosus sp. n., the amphotericin-producing organism. J Bacteriol. 1963;85:436–9.

    Article  CAS  Google Scholar 

  2. Aversa F, Busca A, Candoni A, Cesaro S, Girmenia C, Luppi M, et al. Liposomal amphotericin B (AmBisome®) at beginning of its third decade of clinical use. J Chemother. 2017;29:131–43.

    Article  CAS  Google Scholar 

  3. Stone NR, Bicanic T, Salim R, Hope W. Liposomal amphotericin B (AmBisome(®)): a review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs. 2016;76:485–500.

    Article  CAS  Google Scholar 

  4. Uchida R, Kondo A, Yagi A, Nonaka K, Masuma R, Kobayashi K, et al. Simpotentin, a new potentiator of amphotericin B activity against Candida albicans, produced by Simplicillium minatense FKI-4981. J Antibiot. 2019;72:134–40.

    Article  CAS  Google Scholar 

  5. Fukuda T, Nagai K, Yagi A, Kobayashi K, Uchida R, Yasuhara T, et al. Nectriatide, a potentiator of amphotericin B activity from Nectriaceae sp. BF-0114. J Nat Prod. 2019;82:2673–81.

    Article  CAS  Google Scholar 

  6. Bock K, Lundt I, Pedersen C. Assignment of anomer structure to carbohydrates through geminal 13C-1H coupling constants. Tetrahedron Lett. 1973;13:1037–40.

    Article  Google Scholar 

  7. Kohno J, Nishio M, Sakurai M, Kawano K, Hiramatsu H, Kameda N, et al. Isolation and structure determination of TMC-151s: Novel polyketide antibiotics from Gliocladium catenulatum Gilman & Abbott TC 1280. Tetrahedron 1999;55:7771–86.

    Article  CAS  Google Scholar 

  8. Tanaka T, Nakashima T, Ueda T, Tomii K, Kouno I. Facile discrimination of aldose enantiomers by reversed-phase HPLC. Chem Pharm Bull. 2007;55:899–901.

    Article  CAS  Google Scholar 

  9. Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts. 3rd ed. CLSI document M27-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.

  10. Clinical and Laboratory Standards Institute (CLSI): Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard CLSI document M38-A2. 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.

  11. Luo J, Walsh E, Blystone D, Zhang N. Five new Pseudophialophora species from grass roots in the oligotrophic pine barrens ecosystem. Fungal Biol. 2015;119:1205–15.

    Article  Google Scholar 

  12. Wang B, You, King JB, Cai S, Park E, Powell DR, et al. Polyketide glycosides from Bionectria ochroleuca inhibit Candida albicans biofilm formation. J Nat Prod. 2014;77:2273–9.

    Article  CAS  Google Scholar 

  13. Kasai Y, Komatsu K, Shigemori H, Tsuda M, Mikami Y, Kobayashi J. Cladionol A, a polyketide glycoside from marine-derived fungus Gliocladium species. J Nat Prod. 2005;68:777–9.

    Article  CAS  Google Scholar 

  14. Kohno J, Asai Y, Nishio M, Sakurai M, Kawano K, Hiramatsu H, et al. Komatsubara S. TMC-171A, B, C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282. J Antibiot. 1999;52:1114–23.

    Article  CAS  Google Scholar 

  15. Kumazawa S, Kanda M, Utagawa M, Chiba N, Ohtani H, Mikawa T. MK7924, a novel metabolite with nematocidal activity from Coronophora gregaria. J Antibiot. 2003;56:652–4.

    Article  CAS  Google Scholar 

  16. Tomoda H, Ohyama Y, Abe T, Tabata N, Namikoshi M, Yamaguchi Y, et al. Roselipins, inhibitors of diacylglycerol acyltransferase, produced by Gliocladium roseum KF-1040. J Antibiot. 1999;52:689–94.

    Article  CAS  Google Scholar 

  17. Tabata N, Ohyama Y, Tomoda H, Abe T, Namikoshi M, Ōmura S. Structure elucidation of roselipins, inhibitors of diacylglycerol acyltransferase produced by Gliocladium roseum KF-1040. J Antibiot. 1999;52:815–26.

    Article  CAS  Google Scholar 

  18. Ishijima H, Uchida R, Ohtawa M, Kondo A, Nagai K, Shima K, et al. Simplifungin and valsafungins, antifungal antibiotics of fungal origin. J Org Chem. 2016;81:7373–83.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We express our thanks to Dr. Kenichiro Nagai and Ms. Noriko Sato of the School of Pharmacy, Kitasato University for measurements of NMR and mass spectra. This work was supported by JSPS KAKENHI Grant Numbers 16H05095 (to RU) and 21310146 (to HT).

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Authors and Affiliations

  1. Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University. 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan

    Akiho Yagi & Ryuji Uchida

  2. Microbial Chemistry and Medicinal Research Laboratories, Graduate School of Pharmaceutical Sciences, Kitasato University. 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Keisuke Kobayashi & Hiroshi Tomoda

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  1. Akiho Yagi
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  2. Ryuji Uchida
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Correspondence to Ryuji Uchida or Hiroshi Tomoda.

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41429_2019_276_MOESM1_ESM.doc

Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by <i>Pseudophialophora</i> sp. BF-0158

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Yagi, A., Uchida, R., Kobayashi, K. et al. Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by Pseudophialophora sp. BF-0158. J Antibiot 73, 211–223 (2020). https://doi.org/10.1038/s41429-019-0276-7

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