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. 2022 Oct 28;20(11):679.
doi: 10.3390/md20110679.

Discovery of p-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus Aspergillus sp. ITBBc1

Zhikai Guo  1 , Ailiman Abulaizi  2 , Ling Huang  3 , Zijun Xiong  1 , Shiqing Zhang  1 , Tianmi Liu  4 , Rong Wang  5
Affiliations

Discovery of p-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus Aspergillus sp. ITBBc1

Zhikai Guo et al. Mar Drugs. .

Abstract

Chemical investigation of the fermentation extract of the coral-associated fungus Aspergillus sp. ITBBc1 led to the discovery of five unreported p-terphenyl derivatives, sanshamycins A-E (1-5), together with five previously described analogues, terphenyllin (6), 3-hydroxyterphenyllin (7), candidusin A (8), 4,5-dimethoxycandidusin A (9), and candidusin C (10). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound 1 represents the first example of p-terphenyls with an aldehyde substitution on the benzene ring. Compounds 2-4 feature varying methoxyl and isopentenyl substitutions, while compound 5 features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of p-terphenyl natural products. Compounds 1-6 and 9 were evaluated for their inhibitory activity against type 4 phosphodiesterase (PDE4), which is a fascinating drug target for treatment of inflammatory, respiratory, and neurological diseases. Compound 3 was the most potent and exhibited PDE4D inhibitory activity with an IC50 value of 5.543 µM.

Keywords: Aspergillus sp.; coral-associated fungus; natural products; p-terphenyls; phosphodiesterase PDE4D inhibitor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The structures of 1–10.
Figure 2
Figure 2
Key HMBC, 1H-1H COSY and ROESY correlations of 1–5.
See this image and copyright information in PMC

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