Chlorinated Dehydrocurvularins and Alterperylenepoxide A from Alternaria sp. AST0039, a Fungal Endophyte of Astragalus lentiginosus

  • J Nat Prod. 2017 Feb 24;80(2):427-433. doi: 10.1021/acs.jnatprod.6b00960.
Bharat P Bashyal  1 ,  E M Kithsiri Wijeratne  1 ,  Joseph Tillotson  2 ,  A Elizabeth Arnold  3 ,  Eli Chapman  2 ,  A A Leslie Gunatilaka  1
Affiliations
  • 1. Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona , 250 E. Valencia Road, Tucson, Arizona 85706, United States.
  • 2. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , Tucson, Arizona 85721, United States.
  • 3. School of Plant Sciences, College of Agriculture and Life Sciences, University of Arizona , Tucson, Arizona 85721, United States.
PMID: 28139929 DOI: 10.1021/acs.jnatprod.6b00960
Abstract

Investigation of Alternaria sp. AST0039, an endophytic fungus obtained from the leaf tissue of Astragalus lentiginosus, led to the isolation of (-)-(10E,15S)-4,6-dichloro-10(11)-dehydrocurvularin (1), (-)-(10E,15S)-6-chloro-10(11)-dehydrocurvularin (2), (-)-(10E,15S)-10(11)-dehydrocurvularin (3), and alterperylenepoxide A (4) together with scytalone and α-acetylorcinol. Structures of 1 and 4 were established from their spectroscopic data, and the relative configuration of 4 was determined with the help of nuclear Overhauser effect difference data. All metabolites were evaluated for their cytotoxic activity and ability to induce heat-shock and unfolded protein responses. Compounds 2 and 3 exhibited cytotoxicity to all five Cancer cell lines tested and increased the level of the pro-apoptotic transcription factor CHOP, but only 3 induced the heat-shock response and caused a strong unfolded protein response.