Bioactive Ascochlorin Analogues from the Marine-Derived Fungus Stilbella fimetaria

• Published in: Marine drugs 2021-01, Vol.19 (2), p.46
• Main Authors: Subko, Karolina, Kildgaard, Sara, Vicente, Francisca, Reyes, Fernando, Genilloud, Olga, Larsen, Thomas O
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Alkenes - isolation & purification; Alkenes - pharmacology; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemistry; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; ascochlorin; bioactivity; Candida albicans - drug effects; Candida albicans - physiology; dereplication; Hypocreales - chemistry; Hypocreales - isolation & purification; meroterpenoids; MS/HRMS; Phenols - chemistry; Phenols - isolation & purification; Phenols - pharmacology; Staphylococcus aureus - drug effects; Staphylococcus aureus - physiology
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md19020046

The marine-derived fungus is a chemically talented fungus producing several classes of bioactive metabolites, including meroterpenoids of the ascochlorin family. The targeted dereplication of fungal extracts by UHPLC-DAD-QTOF-MS revealed the presence of several new along with multiple known ascochlorin analogues ( - ). Their structures and relative configuration were characterized by 1D and 2D NMR. Further targeted dereplication based on a novel 1,4-benzoquinone sesquiterpene derivative, fimetarin A ( ), resulted in the identification of three additional fimetarin analogues, fimetarins B-D ( - ), with their tentative structures proposed from detailed MS/HRMS analysis. In total, four new and eight known ascochlorin/fimetarin analogues were tested for their antimicrobial activity, identifying the analogues with a 5-chloroorcylaldehyde moiety to be more active than the benzoquinone analogue. Additionally, the presence of two conjugated double bonds at C-2'/C-3' and C-4'/C-5' were found to be essential for the observed antifungal activity, whereas the single, untailored bonds at C-4'/C-5' and C-8'/C-9' were suggested to be necessary for the observed antibacterial activity.