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.