Activities of alkoxyalkyl esters of cidofovir (CDV), cyclic CDV, and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine against orthopoxviruses in cell monolayers and in organotypic cultures.
The potencies of several alkoxyalkyl esters of acyclic nucleoside phosphonates against vaccinia virus and cowpox virus were evaluated in cell monolayers and three-dimensional epithelial raft cultures. Prodrugs were at least 20-fold more active than their parent compounds. Octadecycloxyethyl-(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine emerged as the most potent derivative.
Lebeau
Ilya
I
Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, Leuven, Belgium. Robert.Snoeck@rega.kuleuven.be.
Andrei
Graciela
G
Dal Pozzo
Fabiana
F
Beadle
James R
JR
Hostetler
Karl Y
KY
De Clercq
Erik
E
van den Oord
Joost
J
Snoeck
Robert
R
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D000077404:Cidofovir; D003500:Cyclization; D003588:Cytopathogenic Effect, Viral; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004952:Esters; D005347:Fibroblasts / Q000821:virology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology*; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D018155:Orthopoxvirus / Q000187:drug effects*
D000998:Antiviral Agents; D004952:Esters; D063065:Organophosphonates; D003596:Cytosine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D000077404:Cidofovir