Gigobolins A–C, New Ophiobolins with Anticancer Activity from the Phytopathogenic Fungus <i>Drechslera gigantea</i>

Three new sesterterpenoids, gigobolins A to C (<b>1</b>-<b>3</b>), along with six known ophiobolins, were isolated and structurally characterized from the culture filtrate of the phytopathogenic fungus <i>Drechslera gigantea.</i> The structures were elucidated using extensive spectroscopic analysis, including 1D and 2D NMR, and HRESIMS, to disclose A/B ring conformation and reveal rings C and D side chain modifications of the ophiobolin tricyclic core structure. Gigobolins A (<b>1</b>) and B (<b>2</b>) together with known maydispenoid A (<b>9</b>) were evaluated for their antiproliferative activity against aggressive glioblastoma multiforme (GBM) and breast cancer cell lines, with a focus on their efficacy against chemoresistant cancer stem cell (CSC) populations. Notably, gigobolin B (<b>2</b>) and maydispenoid A (<b>9</b>) demonstrated significant activity against both GBM CSCs and multiple breast cancer cell lines. These results establish<i>D. gigantea</i> as a significant source of new anti-CSC agents and further validate the ophiobolin family as a valuable chemical scaffold for future drug development efforts targeting cancer stemness (the inherent ability to self-renew and resist conventional therapies) and therapeutic resistance.