Primacenes: on the way to novel organometallic antimalarials

• Type: Summary of Presentation in a National Conference
• Date: 2010

Authors

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

Conference proceedings National

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

Pages: 35-35

2.º Encontro Nacional de Química Terapêutica

Coimbra, Portugal, 28 a 30 Novembro de 2010

Scientific classification

FOS: Engineering and technology > Chemical engineering

CORDIS: Physical sciences > Chemistry > Applied chemistry > Pharmaceutical chemistry

Other information

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.

Language: English

Type (Professor's evaluation): Scientific