Ether lipid-ester prodrugs of acyclic nucleoside phosphonates: activity against adenovirus replication in vitro.
The acyclic nucleoside phosphonate cidofovir (CDV) and its closely related analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine ([S]-HPMPA) have been reported to have activity against many adenovirus (AdV) serotypes. A new series of orally active ether lipid-ester prodrugs of CDV and of (S)-HPMPA that have slight differences in the structure of their lipid esters were evaluated, in tissue-culture cells, for activity against 5 AdV serotypes. The results indicated that, against several AdV serotypes, the most active compounds were 15-2500-fold more active than the unmodified parent compounds and should be evaluated further for their potential to treat AdV infections in humans.
Hartline
Caroll B
CB
University of Alabama School of Medicine, Birmingham, Alabama 35233, USA.
Gustin
Kortney M
KM
Wan
William B
WB
Ciesla
Stephanie L
SL
Beadle
James R
JR
Hostetler
Karl Y
KY
Kern
Earl R
ER
D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000260:Adenoviruses, Human / Q000187:drug effects* / Q000502:physiology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004952:Esters / Q000737:chemistry; D004986:Ether / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests / Q000379:methods; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004952:Esters; D008055:Lipids; D009705:Nucleosides; D063065:Organophosphonates; D011355:Prodrugs; D004986:Ether; D003596:Cytosine; D000225:Adenine; D000077404:Cidofovir