Primacenes: on the way to novel organometallic antimalarials

• Tipo: Resumo de Comunicação em Conferência Nacional
• Data: 2010

Autores

Joana Matos (Autor) Outra; Filipa Cruz (Autor) Outra; Elia Cabrita (Autor) Outra; Fátima Nogueira (Autor) Outra; Nuno Vale (Autor) FCUP; Rui Moreira (Autor) Outra; Virgílio do Rosário (Autor) Outra; Maria Mota (Autor) Outra; Miguel Prudêncio (Autor) Outra; Paula Gomes (Autor) FCUP

Ata de Conferência Nacional

Título: 2.º Encontro Nacional de Química Terapêutica=2nd National Meeting on Medicinal Chemistry

Páginas: 35-35

2.º Encontro Nacional de Química Terapêutica

Coimbra, Portugal, 28 a 30 Novembro de 2010

Classificação Científica

FOS: Ciências da engenharia e tecnologias > Engenharia química

CORDIS: Ciências Físicas > Química > Química aplicada > Química farmacêutica

Outras Informações

Abstract (EN): Primacenes, novel ferrocene-primaquine conjugates, were synthesized and screened for their activity on both the liver-stage and sporogonic development of Plasmodium berghei. Distinct structural requirements were relevant towards optimal activity against those two different stages of the malaria parasite’s life-cycle. Primacenes obtained by coupling ferrocenoic acid to 8-amino-6- methoxyquinoline (MAQ), primaquine (PQ) or PQ derivatives, while significantly active against Pneumocystis carinii and devoid of cytotoxicity, lacked antimalarial activity in vivo as transmissionblocking agents [1] and were moderately active in vitro against liver stage parasites. Having ascribed such loss of anti-Plasmodium activity to the absence of an aliphatic amine group [2-5], we prepared second-generation primacenes bearing such an aliphatic amine and found them to display transmission-blocking activity comparable to or even superior than that of PQ [6]. Interestingly, direct attachment of an alkylferrocene to MAQ yielded a primacene (BIC-601) that is highly active in vitro against liver stage Plasmodia. In vivo liver-stage activity and oral bioavailability of BIC-601 are now under evaluation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica