Angiogenesis Inhibitors and Anti-Inflammatory Agents from Phoma sp. NTOU4195

J Nat Prod. 2016 Dec 23;79(12):2983-2990. doi: 10.1021/acs.jnatprod.6b00407. Epub 2016 Dec 15.

Abstract

Seven new polyketides, phomaketides A-E (1-5) and pseurotins A3 (6) and G (7), along with the known compounds FR-111142, pseurotins A, A1, A2, D, and F2, 14-norpseurotin A, α-carbonylcarbene, tyrosol, cyclo(-l-Pro-l-Leu), and cyclo(-l-Pro-l-Phe), were purified from the fermentation broth and mycelium of the endophytic fungal strain Phoma sp. NTOU4195 isolated from the marine red alga Pterocladiella capillacea. The structures were established through interpretation of spectroscopic data. The antiangiogenic and anti-inflammatory effects of 1-7 and related analogues were evaluated using human endothelial progenitor cells (EPCs) and lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells, respectively. Of the compounds tested, compound 1 exhibited the most potent antiangiogenic activity by suppressing the tube formation of EPCs with an IC50 of 8.1 μM, and compound 3 showed the most selective inhibitory activity of LPS-induced NO production in RAW264.7 macrophages with an IC50 value of 8.8 μM.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / isolation & purification*
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification*
  • Anti-Inflammatory Agents / pharmacology*
  • Ascomycota / chemistry*
  • Epoxy Compounds / pharmacology
  • Humans
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Marine Biology
  • Mice
  • Molecular Structure
  • Nitric Oxide / biosynthesis
  • Polyketides / chemistry
  • Polyketides / isolation & purification*
  • Polyketides / pharmacology*
  • Spiro Compounds / pharmacology
  • Taiwan

Substances

  • 14-norpseurotin
  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents
  • Epoxy Compounds
  • Lipopolysaccharides
  • Polyketides
  • Spiro Compounds
  • FR 111142
  • Nitric Oxide