Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents

Moaz M. Abdou*, Paul M. O'Neill, Eric Amigues, Magdalini Matziari

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The efficacy of most marketed antimalarial drugs has been compromised by the development of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. This article describes the synthesis and the in vitro antimalarial profiling of antifolate P218 analogues, by exploring a bioisosteric replacement of the carboxylic group by a phosphinic moiety as well as structural isomerization of P218. The detailed synthetic route employed to access the title compounds is described. The listed compounds exhibited low antimalarial activity against drug-resistant strains of P. falciparum including chloroquine-resistant W2.

Original languageEnglish
Article number101539
JournalJournal of Saudi Chemical Society
Volume26
Issue number6
DOIs
Publication statusPublished - Nov 2022

Keywords

  • 2,4-Diaminopyrimidines
  • Antimalarial
  • Bioisosterism
  • Malarial dihydrofolate reductase
  • P218
  • Phosphinic acid

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