Clavariopsins C-I, Antifungal Cyclic Depsipeptides from the Aquatic Hyphomycete Clavariopsis aquatica

  • J Nat Prod. 2019 Jul 26;82(7):1971-1978. doi: 10.1021/acs.jnatprod.9b00366.
Thin Wut Soe  1  2 ,  Chunguang Han  3 ,  Ryosuke Fudou  4 ,  Kenichi Kaida  5 ,  Yuki Sawaki  1 ,  Tomohiko Tomura  1 ,  Makoto Ojika  1
Affiliations
  • 1. Graduate School of Bioagricultural Sciences , Nagoya University , Chikusa-ku, Nagoya 464-8601 , Japan.
  • 2. Department of Chemistry , University of Yangon , Yangon 11041 , Myanmar.
  • 3. Research Center for Materials Science , Nagoya University , Chikusa-ku, Nagoya 464-8602 , Japan.
  • 4. R&D Planning Department , Ajinomoto Co., Inc. , Chuo-ku, Tokyo 104-8315 , Japan.
  • 5. Institute of Life Science , Ajinomoto Co., Inc. , Kawasaki , Kanagawa 210-8681 , Japan.
PMID: 31244144 DOI: 10.1021/acs.jnatprod.9b00366
Abstract

Seven new cyclic depsipeptides, clavariopsins C-I (3-9), together with two known congeners, clavariopsins A and B (1 and 2), were isolated from the aquatic hyphomycete Clavariopsis aquatica. Their planar structures, which consist of nine Amino acids and one α-hydroxy acid, were elucidated by NMR spectroscopy and HRESIMS. The absolute configurations were established by the advanced Marfey's method and chiral-phase HPLC analysis. Their Antifungal and cytotoxic activities were evaluated against six plant pathogenic fungi (Botrytis cinerea, Magnaporthe oryzae, Colletotrichum orbiculare, Fusarium oxysporum, Alternaria alternata, and Aspergillus niger) and a Cancer cell line (HeLa-S3), respectively. The majority of the compounds exhibited potent Antifungal activity against the fungi tested (minimum inhibition dose = 0.01-10 μg/disk) and induced hyphal swelling in A. niger (minimum effective dose = 0.3-3 μg/disk), whereas the compounds exhibited no cytotoxicity toward the Cancer cell line. The results suggest that the clavariopsins could be a promising class of Antifungal agents.