L-Aspartic and l-glutamic acid ester-based ProTides of anticancer nucleosides: Synthesis and antitumoral evaluation

Bioorg Med Chem Lett. 2016 May 1;26(9):2142-6. doi: 10.1016/j.bmcl.2016.03.076. Epub 2016 Mar 22.

Abstract

A series of novel aryloxyphosphoramidate nucleoside prodrugs based on l-aspartic acid and l-glutamic acid as amino acid motif has been synthesized and evaluated for antitumoral activity. Depending on the cancer cell line studied and on the nature of the parent nucleoside compound (gemcitabine, 5-iodo-2'-deoxy-uridine, floxuridine or brivudin), the corresponding ProTides are endowed with an improved or decreased cytotoxic activity.

Keywords: Antitumoral; Nucleosides; ProTides; Prodrugs.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / chemical synthesis
  • Aspartic Acid / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Glutamates / chemical synthesis
  • Glutamates / pharmacology*
  • Humans
  • Nucleosides / chemical synthesis
  • Nucleosides / pharmacology*
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / pharmacology*
  • Prodrugs / chemical synthesis
  • Prodrugs / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Glutamates
  • Nucleosides
  • Organophosphorus Compounds
  • Prodrugs
  • Aspartic Acid