Discovery of p-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus Aspergillus sp. ITBBc1
2022
Zhikai Guo | Ailiman Abulaizi | Ling Huang | Zijun Xiong | Shiqing Zhang | Tianmi Liu | Rong Wang
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&ndash:E (1&ndash: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&ndash: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&ndash: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 µ:M.
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