RESUMO
The chemical composition of total alkaloids from leaves and roots of Guiera senegalensis was investigated. Three beta-carboline alkaloids were purified: in addition to harman and tetrahydroharman, known in roots and leaves, harmalan (dihydroharman) was isolated for the first time from roots of Guiera senegalensis. Guieranone A, a naphthyl butenone, was also purified from leaves and roots. The in vitro antiplasmodial activity and the cytotoxicity of extracts and pure compounds were evaluated. Each total alkaloid extract and beta-carboline alkaloids presented an interesting antiplasmodial activity associated with a low cytotoxicity. Harmalan was less active than harman and tetrahydroharman. Guieranone A showed a strong antiplasmodial activity associated with a high cytotoxicity toward human monocytes. Its cytotoxicity was performed against two cancer cell lines and normal skin fibroblasts in order to study its anticancer potential: guieranone A presented a strong cytotoxicity against each cell strains. Finally, we evaluated the potent synergistic antimalarial interaction between Guiera senegalensis and two plants commonly associated in traditional remedies: Mitragyna inermis and Pavetta crassipes. Three associations evaluated were additive. A synergistic effect was shown between total alkaloids extracted from leaves of Guiera senegalensis and those of Mitragyna inermis. This result justified the traditional use of the plants in combination to treat malaria.
Assuntos
Antimaláricos/farmacologia , Combretaceae , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Rubiaceae , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Butanonas , Carbolinas/farmacologia , Sobrevivência Celular , Sinergismo Farmacológico , Harmalina/análogos & derivados , Harmalina/farmacologia , Harmina/análogos & derivados , Harmina/farmacologia , Células HeLa , Humanos , Concentração Inibidora 50 , Monócitos/efeitos dos fármacos , Naftalenos , Oxindóis , Testes de Sensibilidade Parasitária , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta , Raízes de Plantas , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
An efficient system for the analysis of the total alkaloids extracted from leaves of Mitragyna inermis (Willd.) O. Kuntze (Rubiaceae) by HPLC using a reversed-phase column is described. The chromatographic conditions allowed the separation of indole and oxindole alkaloids in leaf extracts, and the quantification of uncarine D in samples collected in Burkina Faso and Mali. The HPLC method described was validated for its specificity, linearity and precision using an internal standard (naphthalene). The concentrations of uncarine D in various extracts were compared with their in vitro anti-plasmodial activity. The anti-proliferative activity on chloroquine-resistant strain (W2) of Plasmodium falciparum was not correlated with the concentration of uncarine D in leaves.