The backbone of effective highly active antiretroviral therapy regimens for the treatment of HIV infections currently contains at least two nucleosides. Among the features that influence the potency of each component of a regimen and the overall efficacy of the combination are the cellular uptake and bioconversion of nucleoside analogues to their active triphosphate form, and the extent of poss...

Human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitors can be classified into nucleoside and nonnucleoside RT inhibitors. Nucleoside RT inhibitors are converted to active triphosphate analogues and incorporated into the DNA in RT-catalyzed reactions. They act as chain terminators blocking DNA synthesis, since they lack the 3'-OH group required for the phosphodiester bond forma...

The synthesis and in vitro anti-HIV activity of a novel series phosphoramidate pronucleotides including S-pivaloyl-2-thioethyl (tBuSATE) group as biolabile phosphate protecting are reported. Such constructs, obtained through different phosphorus chemistries, characterized by the association two nucleoside analogues linked to atom respectively sugar residue exocyclic amino function nucleobase. I...

UNLABELLED Unlike many cancers that exhibit glycolytic metabolism, high-grade liposarcomas often exhibit low 2[18F]fluoro-2-deoxy-D-glucose uptake by positron emission tomography (PET), despite rapid tumor growth. Here, we used liquid chromatography tandem mass spectrometry to identify carbon sources taken up by liposarcoma cell lines derived from xenograft tumors in patients. Interestingly, we...

Antifolates have been used to treat cancer for the last 50 years and remain the mainstay of many therapeutic regimes. Nucleoside salvage, which depends on plasma membrane transport, can compromise the activity of antifolates. The cardiovascular drug dipyridamole inhibits nucleoside transport and enhances antifolate cytotoxicity in vitro, but its clinical activity is compromised by binding to th...