Cytotoxic shornephines and asterresins from the hydrothermal vent associated fungus Aspergillus terreus CXX-158-20

Abstract

A previously unreported alkaloid, bearing an undescribed 5/7/8 tricyclic heterocyclic skeleton, shornephine D, an undescribed diketomorpholine (DKM) shornephine B, two undescribed diketomorpholine derivatives shornephine C and seco-shornephine B methyl ester, an undescribed indole-isoquinoline alkaloid asterresin C, three undescribed indole alkaloids asterresins A-B and D, together with five known compounds, were isolated from the culture of hydrothermal vent associated fungus Aspergillus terreus CXX-158-20. Their structures were unambiguously determined by nuclear magnetic resonance (NMR), mass spectrometry, Mosher's method, ¹³C NMR calculation in combination with DP4+, and ECD calculations. Shornephine D and asterresin C represent two undescribed heterocyclic skeletons. Asterresin D and giluterrin exhibited cytotoxicity activities with IC₅₀ values of 3.96 μM and 7.97 μM against A549 cell line. Asterresin D exhibited cytotoxicity activities with IC₅₀ values of 12.36 μM and 12.48 μM against Namalwa and U266 cell lines. Asterresin A and giluterrin exhibited synergistic effect with adriamycin against MCF-7 cell line.

Keywords: Alkaloids; Aspergillus terreus; Cytotoxicity; Diketomorpholine; Hydrothermal vent associated fungus; Indole-isoquinoline; Natural products; Trichocomaceae.