RESUMO
In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 µM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia cells. Compounds 3 and 6 showed good selectivity on leukemia cells than normal cells. In future studies 3 should be tested against a panel of drug resistant human cells.
Assuntos
Carbolinas/uso terapêutico , Cinamatos/uso terapêutico , Dioxóis/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Alcaloides Indólicos/uso terapêutico , Leucemia/tratamento farmacológico , Alcamidas Poli-Insaturadas/uso terapêutico , Zanthoxylum/química , Apoptose/efeitos dos fármacos , Carbolinas/química , Carbolinas/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cinamatos/química , Cinamatos/farmacologia , Dioxóis/química , Dioxóis/farmacologia , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/química , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologiaRESUMO
Two new norhopane derivatives namely 3ß,6ß,22-trihydroxy-7ß,11α-di[(4-hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (1) and 3ß,6ß,22-trihydroxy-7ß-[(4-hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (2) together with two previously reported compounds, including a norhopane, 3ß,6ß,11α-trihydroxy-7ß-[(4-hydroxybenzoyl)oxy]-24-norhopa-4(23),17(21)-diene (3) and a norneohopane, (21αH)-24-norneohopa-4(23), 22(29)-diene-3ß,6ß,7ß-triol 7-caffeate (4) were isolated from the root bark of Fagaropsis angolensis. Elucidation of their structures was achieved by spectroscopic (NMR, IR and UV) and spectrometric (HRESIMS) data and by comparison of these data with those of related compounds in the literature. Compounds 1-4 were evaluated for their anti-inflammatory activity by measuring the levels of cytokines, IL-1ß, IL-2, GM-CSF and TNF-α in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC). All tested compounds decreased secretion of IL-1ß and TNF-α. Compounds 2 and 4 caused significant decrease of the production of IL-2, GM-CSF and TNF-α compared to the reference drug, ibuprofen. These findings showed that the root barks of F. angolensis are rich source of norhopane derivatives and further provide a scientific rationale of using this plant in Kenyan folk medicine to relieve pain.
Assuntos
Anti-Inflamatórios/farmacologia , Triterpenos Pentacíclicos/farmacologia , Rutaceae/química , Adulto , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Citocinas/análise , Humanos , Quênia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Estrutura Molecular , Triterpenos Pentacíclicos/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Raízes de Plantas/químicaRESUMO
Two bisbenzylisoquinoline and one hasubanane alkaloids: (-)-pseudocurine (1), (-)-pseudoisocurine (2) and (-)-10-oxoaknadinine (3), were isolated from leaf extract of Stephania abyssinica, a plant used in traditional medicine in South Nyanza region of Kenya. They were characterized using 1D ((1)H, (13)C and DEPT) and 2D (COSY, NOESY, HMQC and HMBC) NMR techniques. (-)-Pseudocurine (1) and (-)-pseudoisocurine (2) exhibited strong to moderate anti-plasmodial activity while (-)-10-oxoaknadinine (3) showed moderate to mild activity.
