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

• Published in: Journal of antibiotics 2020-04, Vol.73 (4), p.211-223
• Main Authors: Yagi, Akiho, Uchida, Ryuji, Kobayashi, Keisuke, Tomoda, Hiroshi
• Format: Article
• Language: English
• Subjects: 631/154/1435/2417; 631/154/309/507; Amphotericin B - chemistry; Amphotericin B - pharmacology; Antifungal agents; Antifungal Agents - chemistry; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; Ascomycota - chemistry; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Candida albicans - drug effects; Drug Synergism; Fermentation; Glycosides - administration & dosage; Glycosides - chemistry; Glycosides - isolation & purification; Glycosides - pharmacology; Life Sciences; Medicinal Chemistry; Microbial Sensitivity Tests; Microbiology; Organic Chemistry; Polyketides - administration & dosage; Polyketides - chemistry; Polyketides - isolation & purification; Polyketides - pharmacology
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-019-0276-7

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 (C 6 -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 .