Acatulides A-G, neuroprotective macrolides from Acaulium album H-JQSF

Abstract

Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites, but the knowledge about the topic remains patchy and superficial. Here we present the chemical characterization of acatulides A−G (1−7) as architecturally unprecedented macrolides from the solid-state culture of Acaulium album H-JQSF, an arthropod-associated fungus. The acatulide structures were elucidated by spectroscopic analysis, modified Mosher's method and single-crystal X-ray diffraction. The plausible biosynthetic pathways for compounds 1−4 are proposed. Interestingly, acatulides B−D (2−4) and G (7) were demonstrated to be neuroprotective against the 1-methyl-4-phenylpyridinium (MPP+)-induced damage to SH-SY5Y cells and nematode Caenorhabditis elegans (C. elegans).