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

Chemical investigation of the fermentation extract of the coral-associated fungus sp. ITBBc1 led to the discovery of five unreported -terphenyl derivatives, sanshamycins A-E (-), together with five previously described analogues, terphenyllin (), 3-hydroxyterphenyllin (), candidusin A (), 4,5-dimethoxycandidusin A (), and candidusin C (). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound represents the first example of -terphenyls with an aldehyde substitution on the benzene ring. Compounds - feature varying methoxyl and isopentenyl substitutions, while compound features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of -terphenyl natural products. Compounds - and 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 was the most potent and exhibited PDE4D inhibitory activity with an IC value of 5.543 µM.