Nectriatide, a Potentiator of Amphotericin B Activity from Nectriaceae sp. BF-0114

  • J Nat Prod. 2019 Oct 25;82(10):2673-2681. doi: 10.1021/acs.jnatprod.8b01056.
Takashi Fukuda  1  2 ,  Kenichiro Nagai  1 ,  Akiho Yagi  3 ,  Keisuke Kobayashi  1 ,  Ryuji Uchida  3 ,  Tadashi Yasuhara  1 ,  Hiroshi Tomoda  1
Affiliations
  • 1. Microbial Chemistry and Medicinal Research Laboratories, Graduate School of Pharmaceutical Sciences , Kitasato University , 5-9-1 Shirokane , Minato-ku, Tokyo 108-8641 , Japan.
  • 2. Department of Fisheries, Faculty of Agriculture and Agricultural Technology and Innovation Research Institute , Kindai University , 3327-204 Nakamachi , Nara 631-8505 , Japan.
  • 3. Department of Natural Product Chemistry , Tohoku Medical and Pharmaceutical University , 4-4-1 Komatsushima , Aoba-ku, Sendai, Miyagi 981-8558 , Japan.
PMID: 31498627 DOI: 10.1021/acs.jnatprod.8b01056
Abstract

A new compound, designated nectriatide (1), was isolated as a potentiator of amphotericin B (AmB) activity against Candida albicans from the culture broth of Nectriaceae sp. BF-0114. This structure was elucidated based on spectroscopic analyses (1D and 2D NMR data), chemical methods, and total synthesis. Compound 1 was a unique cyclotetrapeptide consisting of l-N-methyltyrosine, anthranilic acid, l-alanine, and l-valine. Compound 1 and several synthetic derivatives, including linear peptides, potentiated AmB activity against C. albicans by up to 16-fold (the MIC value of AmB decreased from 0.5 μg/mL to 0.031 μg/mL in combination with test compound).