# Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways

## TL;DR

Researchers discovered new compounds from a fungus that can kill cancer cells by affecting cell cycle and apoptosis pathways.

## Contribution

Identification of five novel emestrin-type compounds with cytotoxic effects via regulation of PI3K/AKT and mitochondrial pathways.

## Key findings

- Five new ETP compounds (prenylemestrins C−G) were isolated and structurally characterized.
- Compound 6 showed moderate cytotoxicity and induced G2/M cell cycle arrest in L1210 cells.
- Compound 6 triggered apoptosis by modulating PI3K/AKT and mitochondrial pathways.

## Abstract

Five novel emestrin-type epipolythiodioxopiperazines (ETPs), prenylemestrins C−G (1–5), along with two known ETPs, prenylemestrin A (6) and prenylemestrin B (7), were obtained from Aspergillus nidulans. Their structures were characterized by spectroscopic data, X-ray crystallographic data, ECD comparisons and calculations. Prenylemestrins C−G (1 − 5) represent a rare class of ETPs, characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety. Notably, compound 6 exhibited moderate cytotoxicity, inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.

The online version contains supplementary material available at 10.1007/s13659-025-00498-8.