Aureoterrolides B‒M: Eremophilane-type sesquiterpenoids isolated from Aspergillus aureoterreus and their cytotoxicity

Abstract

Uncovered by genome sequence analyses, twelve undescribed sesquiterpenoids designated aureoterrolides B‒M, were isolated from the culture broth of the fungus Aspergillus aureoterreus together with two known analogues. They are unusual eremophilanes with an oxidized C-4, of which aureoterrolide J is an unreported furanoeremophilane comprising a 3/6/6/5/3 pentacyclic architecture with a rare 3,6-spiro ring system. Their structures and absolute configurations were unambiguously assigned by extensive spectroscopic method and theoretical ECD calculation. All isolated compounds were evaluated their cytotoxicity, and aureoterrolides A, B, and I-K showed moderate cytotoxic activity against three human cancer cell lines (HL-60, HepG-2, and SKOV-3) with IC₅₀ values ranging from 4.53 ± 0.05 to 24.71 ± 0.16 μM. Among them, aureoterrolide A exhibited activity such close to the positive control and apoptotic effect on HL-60 cells at a concentration of 5.0 μM.

Keywords: Aspergillus aureoterreus; Cytotoxicity; Eremophilane sesquiterpenoids; Structure elucidation.