Imidazolidin-4-one peptidomimetic derivatives of primaquine: Synthesis and antimalarial activity

• Autor(a) principal: Nuno Vale
• Data de Publicação: 2008
• Outros Autores: Joana Matos, Jiri Gut, Fatima Nogueira, Virgilio do Rosario, Philip J Rosenthal, Rui Moreira, Paula Gomes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/82064
• topic: Química; Chemical sciences

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 N(1)-acylation. Thus, 'internal' imidazolidin-4-ones derived from dipeptidyl 8-aminoquinolines represent a new entry in antimalarial structure-activity relationships.