title: Synthesis and antiviral evaluation of cyclic and acyclic 2-methyl-3-hydroxy-4-pyridinone nucleoside derivatives.
abstract: A series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the Vorbrüggen reaction. Iron chelation studies, and antiviral evaluation against a broad panel of viruses, were performed. The pK(a) value of ligand 25 and the stability constant of the corresponding iron(III) complex were compared to those of deferiprone. The pFe(3+) values were found to be similar. Some compounds showed moderate activity against both wild-type HSV-1 and HSV-2, as well as against a thymidine kinase deficient strain of HSV-1. These results suggest a novel mode of action for this group of nucleoside analogues.
authors.affiliation: Laboratoire des Matériaux Moléculaires et des Biomatériaux, GCOM2, UMR CNRS 6114, Université de la Méditerranée, case 901, 163 av. de Luminy, 13288 Marseille Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Barral
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.forename: Michel
authors.initials: M
authors.lastname: Camplo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D000077543:Deferiprone; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D008024:Ligands; D009705:Nucleosides; D011728:Pyridones; C020366:3-hydroxy-4-pyridone; D000077543:Deferiprone