Artemisinin-Derived Dimers Have Greatly Improved Anti-Cytomegalovirus Activity Compared to Artemisinin Monomers
Open Access
- 28 April 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (4), e10370
- https://doi.org/10.1371/journal.pone.0010370
Abstract
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. 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. Artemisinin dimers effectively inhibited CMV replication in human foreskin fibroblasts and human embryonic lung fibroblasts (EC50 for dimer sulfone carbamate and dimer primary alcohol 0.06±0.00 µM and 0.15±0.02 µM 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 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. 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.This publication has 38 references indexed in Scilit:
- Malaria-Infected Mice Live until at Least Day 30 after a New Monomeric Trioxane Combined with Mefloquine Are Administered Together in a Single Low Oral DoseJournal of Medicinal Chemistry, 2009
- Cytomegalovirus Infection Causes an Increase of Arterial Blood PressurePLoS Pathogens, 2009
- Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer CellsJournal of Medicinal Chemistry, 2009
- Cytomegalovirus infection in critically ill patients: a systematic reviewCritical Care, 2009
- Cytomegalovirus Reactivation in Critically Ill Immunocompetent PatientsJAMA, 2008
- Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastomaNeuro-Oncology, 2008
- In Vitro Inhibition of Toxoplasma gondii by Four New Derivatives of ArtemisininAntimicrobial Agents and Chemotherapy, 2006
- Effect of Cell Culture Conditions on the Anticytomegalovirus Activity of MaribavirAntimicrobial Agents and Chemotherapy, 2006
- Retinal and extraocular cytomegalovirus end-organ disease in HIV-infected patients in Europe: a EuroSIDA study, 1994?2001European Journal of Clinical Microbiology & Infectious Diseases, 2004
- FoscarnetDrugs, 1991