Novel Potent Metallocenes against Liver Stage Malaria

• Autor(a) principal: Joana Matos
• Data de Publicação: 2012
• Outros Autores: Filipa P da Cruz, Elia Cabrita, Jiri Gut, Fatima Nogueira, Virgilio E do Rosario, Rui Moreira, Philip J Rosenthal, Miguel Prudencio, Paula Gomes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://repositorio-aberto.up.pt/handle/10216/82067
• topic: Medicina básica; Basic medicine

Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a similar to 45-fold-higher level activity against liver stage parasitemia than that of primaquine.