New 3'-O-aromatic acyl-5-fluoro-2'-deoxyuridine derivatives as potential anticancer agents

Eur J Med Chem. 2016 Jun 10:115:41-52. doi: 10.1016/j.ejmech.2016.03.010. Epub 2016 Mar 4.

Abstract

New aromatic and aliphatic 3'-O-acyl-5-fluoro-2'-deoxyuridine derivatives were synthesized and evaluated as candidates for prodrugs against various cancer cell lines. As the most promising candidate for antimalignant therapeutics was found a dual-acting acyl derivative 7h, which apparently released not only the known anticancer nucleoside, 5-fluoro-2'-deoxyuridine (FdU), but also an additional active metabolite, acetylsalicylic acid, reinforcing thus therapeutic effect of FdU. Promising therapeutic indices showed also some aromatic dicarboxylic acids derivatives decorated with FdU esters (11 and 12).

Keywords: 5-fluoro-2′-deoxyuridine; Anticancer; Double barrelled; Glioblastoma multiforme; Multi decorated; Nucleoside analogues.

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
  • Cells, Cultured
  • Deoxyuridine / analogs & derivatives*
  • Deoxyuridine / chemical synthesis
  • Deoxyuridine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Structure-Activity Relationship

Substances

  • 5-fluoro-2'-deoxyuridine
  • Antineoplastic Agents
  • Prodrugs
  • Deoxyuridine