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. 2022 Sep 21;20(10):591.
doi: 10.3390/md20100591.

Phaeosphamides A and B, Cytotoxic Cyclodecadepsipeptides from the Mangrove-Derived Fungus Phaeosphaeriopsis sp. S296

Siwen Niu  1   2 , Jianlin He  2 , Shuhuan Huang  2 , Shouyuan Wu  1 , Ling Zeng  1 , Juan Wang  2 , Bihong Hong  2 , Ziming Chen  1   3
Affiliations

Phaeosphamides A and B, Cytotoxic Cyclodecadepsipeptides from the Mangrove-Derived Fungus Phaeosphaeriopsis sp. S296

Siwen Niu et al. Mar Drugs. .

Abstract

Chemical examination of the fermented broth of the mangrove-derived fungus Phaeosphaeriopsis sp. S296 resulted in the isolation of two new cyclodecadepsipeptides, namely phaeosphamides A (1) and B (2), as well as one known congener Sch 217048 (3). The structures of new metabolites, including absolute configurations, were established on the basis of extensive spectroscopic data analyses, chemical conversion, and Marfey's method. The 2-hydroxy-3-methylpentanoic acid (Hmp) moiety and pipecolic acid (Pip) unit in structures were rarely discovered in nature. Interestingly, compounds 1-3 are examples of peptides discovered from the fungal genus Phaeosphaeriopsis for the first time. All identified compounds were evaluated for their cytotoxicity against five tumor cell lines of AGS, BEL-7402, HepG2, B16, and BIU87. Among them, compound 1 showed inhibitory activities against these tumor cell lines with IC50 values ranging from 5.14 to 66.38 μM. A further mechanistic investigation found that 1 arrested AGS cells in the G2 phase and induced their apoptosis in a dose-dependent manner.

Keywords: Phaeosphaeriopsis sp.; cyclodecadepsipeptides; cytotoxic activity; marine natural products.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of compounds 1–3 from Phaeosphaeriopsis sp. S296.
Figure 2
Figure 2
Selected COSY, HMBC, and REOSY correlations of 1 and 2.
Figure 3
Figure 3
Cytotoxicity of compounds 1–3 against cancer cell lines of AGS (A), BEL-7402 (B), HepG2 (C), B16 (D), and BIU87 (E). * p < 0.05, ** p < 0.01, **** p < 0.0001 vs. Normal.
Figure 4
Figure 4
Compound 1 inhibited AGS cell proliferation with the concentration range from 0 to 10 μM.
Figure 5
Figure 5
(A) Compound 1 induces cell cycle arrest of AGS cells at G2 phase. (B) Compound 1 induces apoptosis of AGS cells. Cells were treated with 1 at the concentration range from 0 to 10 μM for 24 h. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. Normal.
See this image and copyright information in PMC

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