Expedited access to vinaxanthone and chemically edited derivatives possessing neuronal regenerative effects through ynone coupling reactions

ACS Chem Neurosci. 2015 Apr 15;6(4):542-50. doi: 10.1021/cn500237z. Epub 2015 Feb 10.

Abstract

The natural product vinaxanthone has demonstrated a remarkable capability to promote nerve growth following injury or transplantation. In rats following total transection of the spinal cord delivery of vinaxanthone enhanced axonal regeneration, remyelination and angiogenesis at the site of injury all leading to an improved reinstatement of motor function. Through the development of a new ynone coupling reaction, chemically edited derivatives of vinaxanthone have been prepared and studied for improved activity. The coupling reaction allows rapid access to new derivatives, wherein n ynone precursors provide n(2) vinaxanthone analogues. These compounds have been tested for their ability to promote neuronal regrowth using laser axotomy, severing axonal connections in Caenorhabditis elegans. This precise microsurgery using C. elegans allows a new in vivo approach for medicinal chemistry based optimization of neuronal growth promoting compounds.

Keywords: C. elegans; Vinaxanthone; analogue synthesis; laser axotomy; regeneration; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / pathology
  • Caenorhabditis elegans
  • Chromones / chemical synthesis
  • Chromones / chemistry
  • Dimerization
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Lasers
  • Microsurgery
  • Molecular Structure
  • Nerve Regeneration / drug effects
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Water / chemistry
  • Xanthones / chemical synthesis*
  • Xanthones / chemistry
  • Xanthones / pharmacology*

Substances

  • Chromones
  • Neuroprotective Agents
  • Xanthones
  • xanthofulvin
  • Water
  • vinaxanthone