Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1365028 | Bioorganic & Medicinal Chemistry Letters | 2008 | 4 Pages |
The synthesis of imidazolidin-4-one derivatives of primaquine containing the five-membered ring at the C-terminus of a dipeptide backbone coupled to the parent drug is described. These peptidomimetic derivatives were active against a chloroquine-resistant Plasmodium falciparum strain and inhibited the development of the sporogonic cycle of Plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. The novel imidazolidin-4-ones are extremely stable, both in human plasma and in pH 7.4 buffer, as a result of N1-acylation. Thus, ‘internal’ imidazolidin-4-ones derived from dipeptidyl 8-aminoquinolines represent a new entry in antimalarial structure–activity relationships.
Graphical abstractThe synthesis and antimalarial activity of imidazolidin-4-one peptidomimetic derivatives of primaquine is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide