1. Antivaccinia activities of acyclic nucleoside phosphonate derivatives in epithelial cells and organotypic cultures.
- Author
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Snoeck R, Holý A, Dewolf-Peeters C, Van Den Oord J, De Clercq E, and Andrei G
- Subjects
- Adenine analogs & derivatives, Cell Survival drug effects, Epithelial Cells drug effects, Humans, Keratinocytes drug effects, Keratinocytes virology, Models, Theoretical, Molecular Weight, Organ Culture Techniques, Structure-Activity Relationship, Vaccinia virology, Adenine chemical synthesis, Adenine pharmacology, Antiviral Agents chemical synthesis, Antiviral Agents pharmacology, Epithelial Cells virology, Nucleosides chemical synthesis, Nucleosides pharmacology, Organophosphonates chemical synthesis, Organophosphonates pharmacology, Organophosphorus Compounds chemical synthesis, Organophosphorus Compounds pharmacology, Vaccinia drug therapy, Vaccinia virus drug effects
- Abstract
Organotypic "raft" cultures of epithelial cells allow the reconstitution of a skin equivalent that is easily infectible with different viruses with cutaneous tropism. Among these, poxvirus and particularly vaccinia virus (VV) are good candidates for use in antiviral tests, giving histological pictures comparable to those observed in humans infected with smallpox. Therefore, we decided to evaluate a series of phosphonate derivatives for their ability to inhibit VV growth in epithelial cell monolayers, and the most powerful derivatives were tested in the organotypic cultures. The most active compound was 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA], followed by 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine, cyclic (S)-HPMPA, 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC; cidofovir, Vistide], and cyclic (S)-HPMPC. Cidofovir, which is on the market for the treatment of human cytomegalovirus retinitis in immunocompromised patients, is potentially a good candidate for the treatment of a poxvirus outbreak, in the absence of any vaccination.
- Published
- 2002
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