RESUMO
The acetone extract of the root bark of Erythrina burttii showed in vitro antiplasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC(50) values of 0.97 ± 0.2 and 1.73 ± 0.5 µg/ml respectively. The extract also had radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical with an EC(50) value of 12.0 µg/ml. The isoflav-3-enes burttinol-A and burttinol-C, and the 2-arylbenzofuran derivative burttinol-D were identified as the most active antiplasmodial (IC(50)<10 µM) and free radical scavenging (EC(50)ca. 10 µM) principles. The acetone extract of E. burttii at 800 mg/kg/day, in a 4-day Plasmodium berghei ANKA suppressive test, showed in vivo antimalarial activity with 52% chemosuppression. In the same in vivo test, marginal activities were also observed for the extracts of the root and stem bark of Erythrina abyssinica and the root bark of Erythrina sacleuxii.
Assuntos
Antimaláricos/farmacologia , Erythrina/química , Flavonoides/farmacologia , Sequestradores de Radicais Livres/farmacologia , Malária/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/química , Flavonoides/química , Sequestradores de Radicais Livres/química , Humanos , Malária/parasitologia , Masculino , Camundongos , Testes de Sensibilidade Parasitária , Fitoterapia , Extratos Vegetais , Raízes de Plantas/química , Resultado do TratamentoRESUMO
The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50) = 0.9-3 µg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50) = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three--nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.
Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quinonas/farmacologia , Rubiaceae/química , Antraquinonas/isolamento & purificação , Antraquinonas/farmacologia , Concentração Inibidora 50 , Extratos Vegetais/química , Raízes de Plantas , Quinonas/isolamento & purificaçãoRESUMO
Ferroquine (FQ), a chloroquine (CQ) analog, is being developed to treat persons with Plasmodium falciparum malaria. In 146 P. falciparum field isolates from western Kenya, we measured 50% inhibitory concentrations (IC(50); nM) of CQ and FQ by a SYBR Green I in vitro assay. Reference clones included W2 (CQ resistant) and D6 (CQ sensitive). Mutation analysis was done for P. falciparum CQ-resistance transporter gene (Pfcrt K76T). Median IC(50) values for FQ were lower than CQ for field isolates and the W2 clone (both P < 0.05). The Pfcrt mutation (76T), which was detected in > 80% of isolates, conferred higher CQ IC(50) values (P < 0.05) and modestly lower FQ IC(50) values (P < 0.05), versus Pfcrt wild type (K76). FQ is more potent than CQ against CQ-resistant P. falciparum field isolates and the W2 clone, and is less affected by Pfcrt 76T. These findings support the notion that FQ could be useful in treating persons with P. falciparum malaria.