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

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 ). (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.