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PLoS One. 2010 Apr 28;5(4):e10370. doi: 10.1371/journal.pone.0010370.

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

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  • 1Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. boger@jhmi.edu

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 (EC(50) for dimer sulfone carbamate and dimer primary alcohol 0.06+/-0.00 microM and 0.15+/-0.02 microM 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 microM concentrations) which was significantly less than the inhibition achieved with artemisinin dimers (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.

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