Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers

Ravit Arav-Boger, Ran He, Chuang Jiun Chiou, Jianyong Liu, Lauren Woodard, Andrew Rosenthal, Lorraine Jones-Brando, Michael Forman, Gary Posner

Research output: Contribution to journalArticle

Abstract

Background: Artesunate, an artemisinin-derived monomer, was reported to inhibit Cytomegalovirus (CMV) replication. We aimed to compare the in-vitro anti-CMV activity of several artemisinin-derived monomers and newly synthesized artemisinin dimers. Methods: Four artemisinin monomers and two novel artemisinin-derived dimers were tested for anti-CMV activity in human fibroblasts infected with luciferase-tagged highly-passaged laboratory adapted strain (Towne), and a clinical CMV isolate. Compounds were evaluated for CMV inhibition and cytotoxicity. Results: Artemisinin dimers effectively inhibited CMV replication in human foreskin fibroblasts and human embryonic lung fibroblasts (EC50 for dimer sulfone carbamate and dimer primary alcohol 0.0660.00 ±M and 0.1560.02 ±M respectively, in human foreskin fibroblasts) with no cytotxicity at concentrations required for complete CMV inhibition. All four artemisinin monomers (artemisinin, artesunate, artemether and artefanilide) shared a similar degree of CMV inhibition amongst themselves (in μM concentrations) which was significantly less than the inhibition achieved with artemisinin dimmers (P<0.0001). Similar to monomers, inhibition of CMV with artemisinin dimers appeared early in the virus life cycle as reflected by decreased expression of the immediate early (IE1) protein. & Conclusions: Artemisinin dimers are potent and non-cytotoxic inhibitors of CMV replication. These compounds should be studied as potential therapeutic agents for the treatment of CMV infection in humans.

Original languageEnglish (US)
Article numbere10370
JournalPloS one
Volume5
Issue number4
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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