Bioactive Phenylalanine Derivatives and Cytochalasins from the Soft Coral-Derived Fungus, Aspergillus elegans

Cai-Juan Zheng,Chang-Yun Wang,Min Chen,Dong-Lin Zhao,Kai-Ling Wang,Lu-Yong Wu,Chang-Lun Shao,Guang-Ying Chen,Xue-Ping Sun

doi:10.3390/md11062054

Cai-Juan Zheng, Chang-Yun Wang + Show 7 more

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https://doi.org/10.3390/md11062054

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Abstract

One new phenylalanine derivative 4′-OMe-asperphenamate (1), along with one known phenylalanine derivative (2) and two new cytochalasins, aspochalasin A1 (3) and cytochalasin Z24 (4), as well as eight known cytochalasin analogues (5–12) were isolated from the fermentation broth of Aspergillus elegans ZJ-2008010, a fungus obtained from a soft coral Sarcophyton sp. collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods. The absolute configuration of 1 was determined by chemical synthesis and Marfey’s method. All isolated metabolites (1–12) were evaluated for their antifouling and antibacterial activities. Cytochalasins 5, 6, 8 and 9 showed strong antifouling activity against the larval settlement of the barnacle Balanus amphitrite, with the EC50 values ranging from 6.2 to 37 μM. This is the first report of antifouling activity for this class of metabolites. Additionally, 8 exhibited a broad spectrum of antibacterial activity, especially against four pathogenic bacteria Staphylococcus albus, S. aureus, Escherichia coli and Bacillus cereus.

Highlights

Marine-derived fungi have proven to be a promising source of structurally novel and biologically active secondary metabolites that have become interesting and significant resources for drug discovery [1]
Its molecular formula was established as C33H32N2O5 (19 degrees of unsaturation) from HRESIMS, combined with 1H and 13C NMR
C-16, δC 72.8 (C) for C-18 in [11]-cytochalasa-6(12),13,19-triene-1,21-dione-7,18-dihydroxy-16, 18-dimethyl-10-phenyl-(7S*,13E,16S*,18S*,19E)]. These results indicated that the two compounds shared the same macrocyclic moiety, and these were confirmed by other known cytochalasins based on the shared biogenesis

Summary

Introduction

Marine-derived fungi have proven to be a promising source of structurally novel and biologically active secondary metabolites that have become interesting and significant resources for drug discovery [1]. The genus Aspergillus has been known to be a major contributor to the bioactive secondary metabolites of marine fungal origin, for example, antibacterial bisabolene-type sesquiterpenoids from sponge-derived fungus, Aspergillus sp. In our search for new antibacterial, cytotoxic and antifouling natural products from marine fungi in the South China Sea, we have found several bioactive compounds, including sesquiterpenoids, quinolinone alkaloids, azaphilone derivatives, resorcylic acid lactones and anthraquinone derivatives, from marine fungi through the bioassay-guided isolation [2,7,8,9,10,11,12]. Bioassay-guided fractionation of the bioactive extract led to the isolation of one new phenylalanine derivative, 4′-OMe-asperphenamate (1), together with one known phenylalanine derivative asperphenamate (2) [13,14] and two new cytochalasins, aspochalasin A1 (3)

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