Immunosuppressive ergosterol-emodin hybrids from the endophytic Penicillium sp. XB152

Ergostemodins A-D (1-4), four unprecedented heterodimers of ergosterol and emodin units featuring a unique 6/6/6/5/6/6/5/6 octacyclic skeleton, along with an unreported ergosterol, penicillisterene A (5), and a known ergosterol, acrocalysterol C (6), were isolated from the endophytic fungus Penicillium sp. XB152. Their structures were established by extensive spectroscopic analysis and single-crystal X-ray diffraction. A plausible biosynthetic pathway involving an intermolecular Diels-Alder reaction was proposed for 1-4. Compounds 1-6 were immunosuppressive against concanavalin A (ConA)-induced T cell proliferation and Lipopolysaccharide (LPS)-induced B cell proliferation, with EC₅₀ values ranging from 5.80 to 27.97 μM and from 5.44 to 25.66 μM, respectively. Notably, compound 1 displayed moderate cytotoxicity against five human cancer cell lines (HT29, MCF-7, HeLa, HepG2, and A549) with IC₅₀ values ranging from 11.53 to 24.74 μM, while compound 5 showed moderate cytotoxicity against HT29, HeLa, and A549 cells, with IC₅₀ values ranging from 16.82 to 25.63 μM.