Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers.
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 dimer...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2860993?pdf=render |
| _version_ | 1819138256835444736 |
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| author | Ravit Arav-Boger Ran He Chuang-Jiun Chiou Jianyong Liu Lauren Woodard Andrew Rosenthal Lorraine Jones-Brando Michael Forman Gary Posner |
| author_facet | Ravit Arav-Boger Ran He Chuang-Jiun Chiou Jianyong Liu Lauren Woodard Andrew Rosenthal Lorraine Jones-Brando Michael Forman Gary Posner |
| author_sort | Ravit Arav-Boger |
| collection | DOAJ |
| description | 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 (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.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. |
| first_indexed | 2024-12-22T11:03:53Z |
| format | Article |
| id | doaj.art-8a8cda679eb447d0b904cecbb704a0ee |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:03:53Z |
| publishDate | 2010-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8a8cda679eb447d0b904cecbb704a0ee2022-12-21T18:28:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1037010.1371/journal.pone.0010370Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers.Ravit Arav-BogerRan HeChuang-Jiun ChiouJianyong LiuLauren WoodardAndrew RosenthalLorraine Jones-BrandoMichael FormanGary PosnerArtesunate, 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 (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.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.http://europepmc.org/articles/PMC2860993?pdf=render |
| spellingShingle | Ravit Arav-Boger Ran He Chuang-Jiun Chiou Jianyong Liu Lauren Woodard Andrew Rosenthal Lorraine Jones-Brando Michael Forman Gary Posner Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. PLoS ONE |
| title | Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. |
| title_full | Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. |
| title_fullStr | Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. |
| title_full_unstemmed | Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. |
| title_short | Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. |
| title_sort | artemisinin derived dimers have greatly improved anti cytomegalovirus activity compared to artemisinin monomers |
| url | http://europepmc.org/articles/PMC2860993?pdf=render |
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