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Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2021

Author names and affiliations

Anne-Laure Villard
  • Fonction : Auteur
Anne-Marie Aubertin
  • Fonction : Auteur
Christian Périgaud
  • Fonction : Auteur
  • PersonId : 1115168

Résumé

The synthesis and in vitro anti-HIV activity of a novel series of phosphoramidate pronucleotides including a S-pivaloyl-2-thioethyl (tBuSATE) group as biolabile phosphate protecting group are reported. Such constructs, obtained through different phosphorus chemistries, are characterized by the association of two different anti-HIV nucleoside analogues linked to the phosphorus atom respectively by the sugar residue and the exocyclic amino function of the nucleobase. In vitro, comparative anti-HIV evaluation demonstrates that such original prodrugs are able to allow the efficient intracellular combination release of a 5'-mononucleotide as well as another nucleoside analogue. In human T4-lymphoblastoid cells, the pronucleotide 1 shows remarkable antiviral activity with an EC50 in the nanomolar range (0.6 ηM) and without additional cytotoxicity. In addition, these two pronucleotide models exhibit higher selectivity index than the equimolar mixture of their constitutive nucleoside analogues opening the way to further studies with regard to the current use of drug combinations.
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Dates et versions

hal-03407464 , version 1 (28-10-2021)

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Suzanne Peyrottes, Anne-Laure Villard, Anne-Marie Aubertin, Christian Périgaud. Author names and affiliations. European Journal of Medicinal Chemistry, 2021, 216, pp.113315. ⟨10.1016/j.ejmech.2021.113315⟩. ⟨hal-03407464⟩
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