Synthesis and Structure&-Activity Relationships of the Novel Antimalarials 5-Pyridinyl-4(1H)-Pyridones Articles uri icon

authors

  • BUENO, JOSE M.
  • LEON, MARIA L.
  • CALDERON, FELIX
  • CHICHARRO, JESUS
  • ROSA, JUAN C. DE LA
  • DIAZ, BEATRIZ
  • FERNANDEZ, JORGE
  • FIANDOR, JOSE M.
  • FRAILE, MARIA T.
  • GARCIA, MERCEDES
  • HERREROS, ESPERANZA
  • GARCIA-PEREZ, ADOLFO
  • LORENZO, MILAGROS
  • MALLO, ARACELI
  • PUENTE, MARGARITA
  • FERRER BAZAGA, SANTIAGO
  • SAADEDDIN, ANAS
  • ANGULO BARTUREN, ÍÑIGO
  • RURROWS, JEREMY N.

publication date

  • April 2018

start page

  • 3422

end page

  • 3435

issue

  • 8

volume

  • 61

International Standard Serial Number (ISSN)

  • 0022-2623

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

abstract

  • Malaria is still one of the most prevalent parasitic infections in the world, with half of the world's population at risk for malaria. The effectiveness of current antimalarial therapies, even that of the most recent class of antimalarial drugs (artemisinin-combination therapies, ACTs), is under continuous threat by the spread of resistant Plasmodium strains. As a consequence, there is still an urgent requirement for new antimalarial drugs. We previously reported the identification of 4(1H)-pyridones as a novel series with potent antimalarial activities. The low solubility was identified as an issue to address. In this paper, we describe the synthesis and biological evaluation of 4(1H)-pyridones with potent antimalarial activities in vitro and in vivo and improved pharmacokinetic profiles. Their main structural novelties are the presence of polar moieties, such as hydroxyl groups, and the replacement of the lipophilic phenyl rings with pyridines on their lipophilic side chains.

subjects

  • Biology and Biomedicine

keywords

  • antimicrobial agents; mixtures; reaction products; solutions; vacuum