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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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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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