RESUMO
The aim of this study was to synthesize a series of ferrocenyl 4-aminoquinolines and to evaluate their activities against Plasmodium falciparum F32 (chloroquine-sensitive) and FCB1 and K1 (chloroquino-resistant). Some of the ferrocenyl compounds exhibited in vitro antiplasmodial activity in the nM range. In particular, (1R,4R)-N1-(7-chloroquinolin-4-yl)-N4-(ferrocenylmethyl)-N4-methylcyclohexane-1,4-diamine 17 presented the lowest IC50 value (26 nM) against CQ-resistant strains.
Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Compostos Ferrosos/síntese química , Compostos Ferrosos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/síntese química , Quinolinas/farmacologia , Antimaláricos/química , Relação Dose-Resposta a Droga , Compostos Ferrosos/química , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinolinas/química , Relação Estrutura-AtividadeRESUMO
AIM OF THE STUDY: As part of a project to identify new compounds active on malarial parasites, we tested the in vitro antiplasmodial activity of nine plants traditionally used to treat malaria symptoms in Haut-Ogooué Province, South-East Gabon. MATERIALS AND METHODS: Dichloromethane and methanolic extracts of each plant were tested for their antiplasmodial activity on two chloroquine-resistant strains of Plasmodium falciparum (FCB and W2), based on lactate dehydrogenase activity. Cytotoxicity was assessed with the MTT test on MRC-5 human diploid embryonic lung cells. RESULTS: The methanolic extract of Staudtia gabonensis and the dichloromethane extract of Adhatoda latibracteata showed high antiplasmodial activity (IC50<1 µg/ml) and low cytotoxicity, with selectivity indexes of about 58.25 and 16.43, respectively. The methanolic extract of Monodora myristica and the dichloromethane extract of Afromomum giganteum also showed promising activity (1Assuntos
Sobrevivência Celular/efeitos dos fármacos
, Malária/tratamento farmacológico
, Medicinas Tradicionais Africanas
, Extratos Vegetais/uso terapêutico
, Plantas Medicinais/química
, Gabão
, Humanos
, Extratos Vegetais/farmacologia
, Plasmodium falciparum/efeitos dos fármacos
, Especificidade da Espécie