An improved route to 19-substituted geldanamycins as novel Hsp90 inhibitors--potential therapeutics in cancer and neurodegeneration

Chem Commun (Camb). 2013 Oct 4;49(76):8441-3. doi: 10.1039/c3cc43457e.

Abstract

19-Substituted geldanamycin derivatives are efficient Hsp90 inhibitors, without the toxicity associated with the other benzoquinone ansamycins, thus giving them potential for use as molecular therapeutics in cancer and neurodegeneration. Here a new method of synthesising these important compounds is reported, eliminating the need for toxic metals and metalloids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzoquinones / chemical synthesis
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Lactams, Macrocyclic / chemical synthesis
  • Lactams, Macrocyclic / chemistry
  • Lactams, Macrocyclic / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Neoplasms / drug therapy*
  • Nerve Degeneration / drug therapy*
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Neuroprotective Agents
  • geldanamycin