Fusaspironols A-E: Steroidal spirostanols from the deep-sea-derived Fusarium inflexum ZEN8 with inhibitory activities against osteoclastogenesis and adipogenic differentiation.

Five previously undescribed polyhydroxylated spirostanols, fusaspironols A-E (1-5), along with eight known compounds (6-13), were isolated from the deep-sea-derived fungus Fusarium inflexum ZEN8. Their structures were elucidated using spectroscopic analysis, GIAO-based NMR calculations, and DP4+ probability analysis. Notably, this represents only the second report of spirostanols of fungal origin. A plausible biosynthetic pathway linking compounds 1-5 to the putative precursor cholesterol in this fungus was proposed. In biological assays, compound 8 significantly inhibited RANKL-induced osteoclastogenesis in bone marrow macrophages, whereas compounds 2, 3, and 7 suppressed adipogenesis in mature bone marrow stromal cells. None of the compounds exhibited detectable cytotoxicity at the tested concentrations, suggesting their potential as lead compounds for anti-osteoporosis drug development.