RESUMO
Stimulation of lysosomal activity and ROS formation in mouse peritoneal macrophages by five triterpene glycosides, typicosides A1 (1), A2 (2), B1 (3), C1 (4) and C2 (5) has been studied and compared with their cytotoxic activities. Glycosides 1-3 possess moderate activities, but the most cytotoxic glycoside 5 is not active. Typicoside C1 (4), with low toxicity, was proved to be the most active concerning stimulation of ROS formation. This is the first example of a triterpene glycoside from sea cucumbers with low cytotoxicity, but which demonstrates a strong immunostimulatory effect on mouse peritoneal macrophages in vitro.
Assuntos
Glicosídeos/farmacologia , Pepinos-do-Mar/química , Triterpenos/farmacologia , Animais , Glicosídeos/química , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Triterpenos/químicaRESUMO
Two novel triterpene holostane nonsulfated pentaosides, kolgaosides A (1) and B (2), and one known, holothurinoside B (3), were isolated from the Arctic sea cucumber Kolga hyalina, the second representative of the family Elpidiidae, order Elasipodida, from which triterpene glycosides have been obtained. The structures of 1 and 2 were elucidated using 1H and 13C NMR and 2D NMR procedures (HSQC, HMBC, COSY, ROESY, TOCSY) and HRESI mass-spectrometry. Kolgaosides A (1) and B (2) demonstrate low cytotoxic activity against the cells of the ascite form of mouse Ehrlich carcinoma and moderate hemolytic activity against mouse erythrocytes, despite the presence of hydroxy groups in the side chains of the aglycones. The glycosides of K. hyalina are similar to those of the Antarctic sea cucumber Rhipidothuria racowitzai Hèrouard, 1901 (=Achlionice violaescupidata) (Elasipodida: Elpidiidae); this may have chemotaxonomic significance.
Assuntos
Glicosídeos/química , Pepinos-do-Mar/química , Triterpenos/química , Animais , Regiões Árticas , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacologia , Glicosídeos/farmacologia , Espectrometria de Massas , Camundongos , Estrutura Molecular , Água do Mar , Triterpenos/farmacologiaRESUMO
In non-cytotoxic concentrations, frondoside A (1) from the sea cucumber Cucumaria okhotensis and cucumarioside A2-2 (2) from C. japonica, as well as their complexes with cholesterol block the activity of membrane transport P-glycoprotein in cells of the ascite form of mouse Ehrlich carcinoma. They prevent in this way an efflux of fluorescent probe Calcein from the cells. Since the blocking of P-glycoprotein activity results in decrease of multidrug resistance, these glycosides and their complexes with cholesterol may be considered as potential inhibitors of multidrug resistance of tumor cells.
