biostudies-literatureLi PFundamental Research Funds for the Central UniversitiesNational Natural Science Foundation of China17https://www.ebi.ac.uk/biostudies/studies/S-EPMC11891114biostudies-literatureUnknown15(1)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.Natural products and bioprospectingEmestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways.PMC11891114821040282024BRA018U22A2038082173706Fu AZhang YXiao YLi PLi QZhu HWei WChen CZhou YQi CfalseEmestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways.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.2025-01-01T00:00:00Z2025 Mar2026-06-01T10:32:34.711Z2025-04-07T07:50:13.058ZS-EPMC118911144005927510.1007/s13659-025-00498-8