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

Three new sesterterpenoids, gigobolins A to C (1–3), along with six known ophiobolins, were isolated and structurally characterized from the culture filtrate of the phytopathogenic fungus Drechslera gigantea. 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 (1) and B (2) together with known maydispenoid A (9) 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 (2) and maydispenoid A (9) demonstrated significant activity against both GBM CSCs and multiple breast cancer cell lines. These results establishD. gigantea 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.