Primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the N-terminus as potential antimalarial prodrugs

Nuno Vale, Fátima Nogueira, Virgílio E. do Rosário, Paula Gomes, Rui Moreira

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the N-terminus were synthesized and evaluated as potential transmission-blocking antimalarial prodrugs. All compounds were hydrolyzed to the parent dipeptide derivative of primaquine in neutral and basic solutions, with half lives ranging from 0.7 to 31 h at 37 °C, depending on the nature of the substituents present in the imidazolidin-4-one moiety and in the C-terminal amino acid directly coupled to primaquine. The antimalarial activity was studied for selected compounds using a model consisting of Plasmodium berghei, BalbC mice and Anopheles stephensi mosquitoes. The imidazolidin-4-one derived from Ala-Ala-primaquine and acetone reduced the transmission of the infection to mosquitoes more efficiently than primaquine as shown by the significant decrease in the number of oocysts in the midguts of the mosquitoes at 10 and 50 μmol/kg when compared to the control.

Original languageEnglish
Pages (from-to)2506-2516
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number6
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Gametocytocidal activity
  • Imidazolidin-4-ones
  • Malaria
  • Primaquine
  • Prodrugs

Fingerprint

Dive into the research topics of 'Primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the N-terminus as potential antimalarial prodrugs'. Together they form a unique fingerprint.

Cite this