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

TL;DR

Scientists discovered new anticancer compounds from a plant-damaging fungus that show promise against resistant cancer cells.

Contribution

Gigobolins A–C are new ophiobolins with antiproliferative activity against cancer stem cells and resistant cancer cell lines.

Findings

Gigobolins A and B, along with maydispenoid A, showed significant antiproliferative activity against glioblastoma and breast cancer cells.

The compounds were effective against chemoresistant cancer stem cell populations.

Drechslera gigantea is identified as a source of potential anti-cancer agents targeting therapeutic resistance.

Abstract

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.

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