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Pro-Apoptotic and Immunostimulatory Tetrahydroxanthone Dimers from the Endophytic Fungus Phomopsis longicolla

Authors
  • Rönsberg, David
  • Debbab, Abdessamad
  • Mándi, Attila
  • Vasylyeva, Vera
  • Böhler, Philip
  • Stork, Björn
  • Engelke, Laura
  • Hamacher, Alexandra
  • Sawadogo, Richard
  • Marc Diederich
  • Wray, Victor
  • Lin, Wenhan
  • Kassack, Matthias U.
  • Janiak, Christoph
  • Scheu, Stefanie
  • Wesselborg, Sebastian
  • Kurtán, Tibor
  • Aly, Amal H.
  • Proksch, Peter
Type
Published Article
Journal
The Journal of Organic Chemistry
Publisher
American Chemical Society
Publication Date
Dec 20, 2013
Volume
78
Issue
24
Pages
12425–12425
Identifiers
DOI: 10.1021/jo402066b
Source
LBMCC
Keywords
License
White

Abstract

Four tetrahydroxanthone dimers (1-4) and four biogenetically related monomers (5-8), including the new derivatives (4-6), were isolated from the endophyte Phomopsis longicolla. The absolute configurations of 2-4 were established for the first time by TDDFT ECD calculations and that of phomoxanthone A (1) was revised by X-ray crystallography. Phomoxanthone A (1) showed the strongest pro-apoptotic activity when tested against a panel of human cancer cell lines, including cisplatin resistant cells, whereas it was up to 100-fold less active against healthy blood cells. It was also the most potent activator of murine T lymphocytes, NK cells and macrophages, suggesting an activation of the immune system in parallel to its pro-apoptotic activity. This dual effect in combating cancer cells could help in fighting resistance during chemotherapy. Preliminary structure activity studies of isolated compounds and derivatives obtained by semisynthesis (9a-11) hinted at the location of the biaryl axis and the presence of acetyl groups as important structural elements for the biological activity of the studied tetrahydroxanthones

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