Molecules (Nov 2018)

Natalenamides A–C, Cyclic Tripeptides from the Termite-Associated <i>Actinomadura</i> sp. RB99

  • Seoung Rak Lee,
  • Dahae Lee,
  • Jae Sik Yu,
  • René Benndorf,
  • Sullim Lee,
  • Dong-Soo Lee,
  • Jungmoo Huh,
  • Z. Wilhelm de Beer,
  • Yong Ho Kim,
  • Christine Beemelmanns,
  • Ki Sung Kang,
  • Ki Hyun Kim

DOI
https://doi.org/10.3390/molecules23113003
Journal volume & issue
Vol. 23, no. 11
p. 3003

Abstract

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In recent years, investigations into the biochemistry of insect-associated bacteria have increased. When combined with analytical dereplication processes, these studies provide a powerful strategy to identify structurally and/or biologically novel compounds. Non-ribosomally synthesized cyclic peptides have a broad bioactivity spectrum with high medicinal potential. Here, we report the discovery of three new cyclic tripeptides: natalenamides A⁻C (compounds 1⁻3). These compounds were identified from the culture broth of the fungus-growing termite-associated Actinomadura sp. RB99 using a liquid chromatography (LC)/ultraviolet (UV)/mass spectrometry (MS)-based dereplication method. Chemical structures of the new compounds (1⁻3) were established by analysis of comprehensive spectroscopic methods, including one-dimensional (1H and 13C) and two-dimensional (1H-1H-COSY, HSQC, HMBC) nuclear magnetic resonance spectroscopy (NMR), together with high-resolution electrospray ionization mass spectrometry (HR-ESIMS) data. The absolute configurations of the new compounds were elucidated using Marfey’s analysis. Through several bioactivity tests for the tripeptides, we found that compound 3 exhibited significant inhibitory effects on 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production. The effect of compound 3 was similar to that of kojic acid, a compound extensively used as a cosmetic material with a skin-whitening effect.

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