Potent antimalarial 4-pyridones with improved physico-chemical properties Articles uri icon

authors

  • Bueno, Jose M.
  • Manzano, Pilar
  • Garcia, Maria C.
  • Chicharro, Jesus
  • Puente, Margarita
  • Lorenzo, Milagros
  • Garcia, Adolfo
  • FERRER BAZAGA, SANTIAGO
  • Gomez, Ruben M.
  • Fraile, Maria T.
  • Lavandera, Jose L.
  • Fiandor, Jose M.
  • Vidal, Jaume
  • Herreros, Esperanza
  • Gargallo Viola, Domingo

publication date

  • September 2011

issue

  • 18

volume

  • 21

abstract

  • Antimalarial 4-pyridones are a novel class of inhibitors of the plasmodial mitochondrial electron transport chain targeting Cytochrome bc1 (complex III). In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form. The strategy of introducing polar hydroxymethyl groups has enabled us to maintain the high levels of antimalarial potency observed for other more lipophilic analogues whilst improving the solubility and the oral bioavailability in pre-clinical species. (copyright) 2011 Elsevier Ltd. All rights reserved.

keywords

  • 4-pyridones; malaria; pharmacokinetic; plasmodium falciparum; solubility