Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors

Eur J Med Chem. 2014 Aug 18:83:498-507. doi: 10.1016/j.ejmech.2014.06.067. Epub 2014 Jun 28.

Abstract

A series of substituted coumarins1-10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human cancer cells (GI50 = 2-30 μM) and induced a high apoptosis level in MCF-7 breast cancer cell line. The molecular signature of hsp90 inhibition was assessed by depletion of the Erα hsp90 client protein.

Keywords: 4TCNA; 6BrCaQ; Apoptosis; Cytotoxicity; Hsp90.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chemistry Techniques, Synthetic
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • MCF-7 Cells
  • Novobiocin / chemical synthesis*
  • Novobiocin / chemistry
  • Novobiocin / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Novobiocin