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Conservation of antiviral activity and improved selectivity in PMEO-DAPym upon pyrimidine to triazine scaffold hopping

AuthorsCastro, Sonia de ; Fernández-Cureses, Gloria ; Andrei, G; Snoeck, R.; Sánchez-Murcia, Pedro A. ; Korban, B.; Gago, Federico ; Balzarini, Jan; Camarasa Rius, María José
Issue Date2015
CitationAntiviral Research 122: 64-68 (2015)
AbstractAcyclic nucleoside phosphonates incorporating 2,4-diaminotriazine (DAT) as a 5-aza-analog of the 2,4-diamino-pyrimidine (DAPym) nucleobase present in PMEO-DAPyms have been synthesized. The lead PMEO-DAT is as inhibitory against HIV, HBV, MSV and VZV replication as the parent PMEO-DAPym and equally inefficient at markedly affecting replication of HSV-1, HSV-2 and HCMV. A rationale for this similar biological profile is proposed on the basis of structural differences in the active site of the viral DNA polymerases. PMEO-DAT is, however, more selective because, unlike PMEO-DAPym, it does not stimulate secretion of β-chemokines in cultured PBMC.
Publisher version (URL)http://dx.doi.org/10.1016/j.antiviral.2015.08.006
Identifiersdoi: 10.1016/j.antiviral.2015.08.006
issn: 1872-9096
e-issn: 1872-9096
Appears in Collections:(IQM) Artículos
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