Glycosphingolipid biosinthetic pathway as target for new antiparasitic drugs Tamara A. Piñero, Malena Landoni, Diana Acosta, Vilma G. Duschak y Alicia S. Couto

TAMARA A. PIÑERO, ; MALENA LANDONI, ; DIANA ACOSTA, ; VILMA G. DUSCHAK ; ALICIA S. COUTO

Potrero de los Funes- San Luis

Congreso; XLVII Reunión Anual de la SAIB; 2011

Sociedad Argentina de Investigacines en Química Orgánica.

Sphingolipids are important components of eukaryotic cells. Besides serving as structural components, they regulate cell proliferation, differentiation, cell migration, signaling, trafficking, cell-cell interactions, etc. Tamoxifen ((Z)-1-(4-(2-(dimethylamino)ethoxyl-phenyl)-1,2-diphenyl-1-butane, TAM), a non steroidal anti-estrogen widely used for the treatment of breast cancer,  has been involved with lipid metabolism in intact cells, however little experimental evidence exist up to date, related to the real effect of this drug in sphingolipid biosynthesis. Continuing with our work on the structure of Trypanosoma cruzi glycoconjugates we have shown that TAM inhibits epimastigote and trypomastigote development. We have performed a metabolic incorporation of NBD-ceramide into parasites treated or not with TAM. Sphingolipids were extracted and purified. TLC analysis showed that neutral sphingolipid biosynthesis was enhanced in treated parasites. When an HPLC analysis was performed, four labelled components were observed and interestingly three of them of the treated parasites presented a double area when compared with the untreated ones. In addition, as it is well known that ceramide induces cell apoptosis, we further analyzed by flow citometry if this even is taking place in T. cruzi.