Artemisinin-derived dimer phosphate esters as potent anti-cytomegalovirus (anti-CMV) and anti-cancer agents: a structure-activity study

Bioorg Med Chem. 2013 Jul 1;21(13):3702-7. doi: 10.1016/j.bmc.2013.04.027. Epub 2013 Apr 22.

Abstract

We recently reported the anti-cancer and anti-cytomegalovirus (CMV) activity of artemisinin-derived trioxane diphenylphosphate dimer 838. To probe the relationship between chemical structure and anti-CMV and anti-cancer activities, we now report synthesis and evaluation of a series of eight new dimer phosphate ester analogs of 838. This series of novel molecules was screened against human foreskin fibroblasts (HFFs) infected with CMV and against the human Jurkat T cell acute lymphoblastic leukemia cell line. This SAR study confirms the very high anti-CMV and anti-cancer potencies of dimer diphenyl phosphate ester 838 without its being toxic to normal cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Artemisinins / chemistry*
  • Artemisinins / pharmacology
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus Infections / drug therapy*
  • Dimerization
  • Esters
  • Humans
  • Jurkat Cells
  • Leukemia / drug therapy*
  • Phosphates / chemistry
  • Phosphates / pharmacology

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Artemisinins
  • Esters
  • Phosphates
  • artemisinin