Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4578-81. doi: 10.1016/j.bmcl.2010.06.016. Epub 2010 Jun 8.

Abstract

Efficient regioselective syntheses of conjugates of folic acid and cytotoxic agents derived from natural epothilones are described. These folate receptor (FR) targeting compounds are water soluble and incorporate a hydrophilic peptide-based spacer unit and a reducible self-immolative disulfide-based linker system between the FR-targeting ligand and the parent drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Disulfides / chemistry
  • Epothilones / chemical synthesis
  • Epothilones / chemistry*
  • Epothilones / pharmacology
  • Folate Receptors, GPI-Anchored / antagonists & inhibitors*
  • Folate Receptors, GPI-Anchored / metabolism
  • Folic Acid / chemical synthesis
  • Folic Acid / chemistry*
  • Folic Acid / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Disulfides
  • Epothilones
  • Folate Receptors, GPI-Anchored
  • Folic Acid