New azaphilones and chlorinated phenolic glycosides from Chaetomium elatum with caspase-3 inhibitory activity

Planta Med. 2012 Oct;78(15):1683-9. doi: 10.1055/s-0032-1315211. Epub 2012 Aug 13.

Abstract

Three new azaphilones, chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3), and two new chlorinated phenolic glycosides, globosumoside A (4) and globosumoside B (5), were isolated from the crude extract of the fungal strain Chaetomium elatum No. 89-1-3-1. Their structures were determined by detailed NMR and MS spectroscopic analyses. The absolute configurations of C-7 in chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3) were assigned by CD experiments, and the absolute configurations of 1 and 2 were established by X-ray crystallography. Compounds 1-3 are the first examples of 7R-configurated azaphilones with a chlorinated isochromen from Chaetomium spp. In addition, compounds 1-3 showed inhibitory activity in the cysteine aspartyl-specific protease-3 (caspase-3) enzymatic assay, with IC₅₀ values of 20.6, 10.9, and 7.9 µM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzopyrans / chemistry
  • Benzopyrans / isolation & purification
  • Benzopyrans / pharmacology*
  • Caspase 3 / drug effects
  • Caspase Inhibitors / chemistry
  • Caspase Inhibitors / isolation & purification
  • Caspase Inhibitors / pharmacology*
  • Cell Extracts / chemistry
  • Cell Extracts / isolation & purification
  • Cell Extracts / pharmacology*
  • Chaetomium / chemistry*
  • Crystallography, X-Ray
  • Glycosides / chemistry
  • Glycosides / isolation & purification
  • Glycosides / pharmacology*
  • Halogenation
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Medicine, Chinese Traditional
  • Models, Molecular
  • Molecular Structure
  • Phenols / chemistry
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Pigments, Biological / chemistry
  • Pigments, Biological / isolation & purification
  • Pigments, Biological / pharmacology*
  • Recombinant Proteins

Substances

  • Benzopyrans
  • Caspase Inhibitors
  • Cell Extracts
  • Glycosides
  • Phenols
  • Pigments, Biological
  • Recombinant Proteins
  • azaphilone
  • Caspase 3