Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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

Similar articles

See all similar articles

Cited by

References

    1. Baillie G.S., Tejeda G.S., Kelly M.P. Therapeutic targeting of 3′,5′-cyclic nucleotide phosphodiesterases: Inhibition and beyond. Nat. Rev. Drug Discov. 2019;18:770–796. doi: 10.1038/s41573-019-0033-4. - DOI - PMC - PubMed
    1. Crocetti L., Floresta G., Cilibrizzi A., Giovannoni M.P. An overview of PDE4 inhibitors in clinical trials: 2010 to early 2022. Molecules. 2022;27:4964. doi: 10.3390/molecules27154964. - DOI - PMC - PubMed
    1. Spina D. PDE4 inhibitors: Current status. Brit. J. Pharmacol. 2008;155:308–315. doi: 10.1038/bjp.2008.307. - DOI - PMC - PubMed
    1. Lin T.-T., Huang Y.-Y., Tang G.-H., Cheng Z.-B., Liu X., Luo H.-B., Yin S. Prenylated coumarins: Natural phosphodiesterase-4 inhibitors from Toddalia asiatica. J. Nat. Prod. 2014;77:955–962. doi: 10.1021/np401040d. - DOI - PubMed
    1. Cheng Z.-B., Deng Y.-L., Fan C.-Q., Han Q.-H., Lin S.-L., Tang G.-H., Luo H.-B., Yin S. Prostaglandin derivatives: Nonaromatic phosphodiesterase-4 inhibitors from the soft coral Sarcophyton ehrenbergi. J. Nat. Prod. 2014;77:1928–1936. doi: 10.1021/np500394d. - DOI - PubMed

MeSH terms

Substances

LinkOut - more resources