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

Author(s): 
Arav-Boger, Ravit
He, Ran
Chiou, Chuang-Jiun
Liu, Jianyong
Woodard, Lauren
Rosenthal, Andrew
Jones-Brando, Lorraine
Forman, Michael
Posner, Gary
Item Type: 
Journal Article
Publication Title: 
PloS One
Journal Abbreviation: 
PLoS ONE
Publication Date: 
2010
Publication Year: 
2010
Pages: 
e10370
Volume: 
5
Issue: 
4
ISSN: 
1932-6203
DOI: 
10.1371/journal.pone.0010370
Library Catalog: 
PubMed
Extra: 
PMID: 20442781 PMCID: PMC2860993

Turabian/Chicago Citation

Ravit Arav-Boger, Ran He, Chuang-Jiun Chiou, Jianyong Liu, Lauren Woodard, Andrew Rosenthal, Lorraine Jones-Brando, Michael Forman and Gary Posner. 2010. "Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers." PloS One 5: 4: e10370. 10.1371/journal.pone.0010370.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1371/journal.pone.0010370 | issn = 1932-6203 | volume = 5 | pages = e10370 | last = Arav-Boger | first = Ravit | coauthors = He, Ran, Chiou, Chuang-Jiun, Liu, Jianyong, Woodard, Lauren, Rosenthal, Andrew, Jones-Brando, Lorraine, Forman, Michael, Posner, Gary | title = Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers | journal = PloS One | date = 2010 | pmid = | pmc = }} </ref>