Efficient synthesis of Hsp90 inhibitor dimers as potential antitumor agents

Bioorg Med Chem. 2010 Aug 1;18(15):5732-7. doi: 10.1016/j.bmc.2010.05.075. Epub 2010 Jun 9.

Abstract

The PU-H58-dimers 13a-15b were efficiently synthesized and their biological properties were evaluated. The copper-catalyzed alkyne azide coupling was effective in simultaneously linking three components via a triazole formation to afford the target dimers. These synthesized dimers exhibited binding affinity to the N-terminal domain of Hsp90, cytotoxicity, and client degradation activity although these activities were comparative or weak comparable with that of the parent compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / chemical synthesis
  • Adenine / toxicity
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Catalysis
  • Cell Line, Tumor
  • Copper / chemistry
  • Dimerization
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Copper
  • Adenine