Trichocyalides A and B, new inhibitors of alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblasts, produced by Trichoderma sp. FKI-5513

J Antibiot (Tokyo). 2012 Nov;65(11):565-9. doi: 10.1038/ja.2012.70. Epub 2012 Sep 5.

Abstract

Two new butenolides, designated trichocyalides A and B, were isolated along with the known compound harzianolide, from the culture broth of Trichoderma sp. FKI-5513 by solvent extraction, ODS column chromatography and HPLC. Their structures were elucidated by several spectral analyses, showing that they have the common skeleton of butenofuranone. Trichocyalides A and B inhibited alkaline phosphatase (ALP) activity, a typical marker enzyme of osteoblastic differentiation (IC(50): 83.0 and 187 μM, respectively), in bone morphogenetic protein (BMP)-stimulated C2C12 myoblasts mutant cells, which stably express BMP receptor activity, whereas harzianolide showed no inhibitory activity against ALP even at 500 μM.

MeSH terms

  • Activin Receptors, Type I / antagonists & inhibitors
  • Activin Receptors, Type I / genetics
  • Alkaline Phosphatase / antagonists & inhibitors*
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Butanes / chemistry
  • Butanes / isolation & purification*
  • Butanes / pharmacology*
  • Cell Line
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology*
  • Genes, Reporter
  • Lactones / chemistry
  • Lactones / isolation & purification*
  • Lactones / pharmacology*
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Molecular Structure
  • Myoblasts / drug effects*
  • Myoblasts / enzymology*
  • Nuclear Magnetic Resonance, Biomolecular
  • Signal Transduction / drug effects
  • Trichoderma / chemistry*
  • Trichoderma / classification
  • Trichoderma / genetics

Substances

  • Anti-Bacterial Agents
  • Bone Morphogenetic Proteins
  • Butanes
  • Enzyme Inhibitors
  • Lactones
  • harzianolide
  • trichocyalide A
  • trichocyalide B
  • Activin Receptors, Type I
  • Acvr1 protein, mouse
  • Alkaline Phosphatase

Associated data

  • GENBANK/AB606411