Discovery of Rearranged Steroids from Cultures of Penicillium soli as Inhibitors of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease characterized by high disability and mortality rates. During our ongoing research on bioactive natural products from fungi, six ergosterol-type steroids (1-6), including five previously unknown compounds, penisterones A-E (1-5), were isolated from cultures of Penicillium soli TJ507, using HSQC-based DeepSAT analysis. The structures of these compounds were elucidated via comprehensive spectroscopic analyses, NMR chemical shift calculations with DP4+ probability analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 1 is the first ergosterol-type natural product with a 14,15-seco framework based on a 1(10→6)-abeo-18,22-cyclosterol core. Compound 6 exhibited antifibrotic activity by suppressing TGF-β1-driven fibroblast activation and extracellular matrix production in NIH/3T3 cells. The same compound alleviated the pathological changes in the bleomycin-induced IPF mice, that might provide a potential lead compound in the drug development for IPF.