Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships

Markus Bohnert, Hans-Wilhelm Nuetzmann, Volker Schroeckh, Fabian Horn, Hans-Martin Dahse, Axel A Brakhage, Dirk Hoffmeister

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The fungal genus Armillaria is unique in that it is the only natural source of melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic acid or its derivatives. This class of natural products is known to exert antimicrobial and cytotoxic effects. Here, we present a refined relationship between the structure and the antimicrobial activity of the melleolides. Using both agar diffusion and broth dilution assays, we identified the Δ(2,4)-double bond of the protoilludene moiety as a key structural feature for antifungal activity against Aspergillus nidulans, Aspergillus flavus, and Penicillium notatum. These findings contrast former reports on cytotoxic activities and may indicate a different mode of action towards susceptible fungi. We also report the isolation and structure elucidation of five melleolides (6'-dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'-chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that treatment with an antifungal melleolide impacts transcription of A. nidulans natural product genes.

Original languageEnglish
Pages (from-to)101-8
Number of pages8
JournalPhytochemistry
Volume105
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antifungal Agents
  • Armillaria
  • Aspergillus
  • Fungi
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Resorcinols
  • Sesquiterpenes
  • Structure-Activity Relationship
  • Journal Article
  • Research Support, Non-U.S. Gov't

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