Synthesis and biological evaluation of novel coumarin-based inhibitors of Cdc25 phosphatases

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5827-30. doi: 10.1016/j.bmcl.2010.07.130. Epub 2010 Aug 3.

Abstract

The cell division cycle 25 (Cdc25) family of proteins are dual specificity phosphatases that activate cyclin-dependent kinase (CDK) complexes, which in turn regulate progression through the cell division cycle. Overexpression of Cdc25 proteins has been reported in a wide variety of cancers; their inhibition may thus represent a novel approach for the development of anticancer therapeutics. Herein we report new coumarin-based scaffolds endowed with a selective inhibition against Cdc25A and Cdc25C, being 6a and 6d the most efficient inhibitors and worthy of further investigation as anticancer agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Coumarins / chemical synthesis*
  • Coumarins / chemistry
  • Coumarins / therapeutic use
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Neoplasms / drug therapy
  • cdc25 Phosphatases / antagonists & inhibitors*
  • cdc25 Phosphatases / metabolism

Substances

  • Antineoplastic Agents
  • Coumarins
  • Enzyme Inhibitors
  • coumarin
  • cdc25 Phosphatases