Síntese de candidatos a inibidores da enzima 5’-metiltioadenosina/S-adenosilhomocisteína nucleosidase, potenciais agentes antiparasitários

Abstract

This thesis, entitled “Synthesis of candidates as inhibitors of the enzyme 5’-methylthioadenosine/S-adenosylhomocysteíne nucleosidase: potential anti-parisitic agents”, concerns the synthesis of novel, potentially active anti-parasitic compounds. For sake of clarity, the thesis is presented in two chapters. Chapter one shows an attempted synthesis of 9-(6’-methylthio-β-D-psicofuranosyl)-adenine, an analogue of 5’-methylthioadenosine (MeSAdo), modified by addition of a hydroxymethyl group at position 1’ of the ribosidic linkage. Many microorganisms, including Plasmodium spp., can use the MeSAdo/AdoHcy nucleosidase enzyme to cleave the ribosidic linkage of the MeSAdo nucleoside into adenine and 5-methylthioribose, a fundamental reaction in the closure of the metabolic cycle of the parasites. "Formula disponível no trabalho completo" The second chapter of this thesis describes the synthesis of analogues of 5-methylthioribose derived from purines, pyrimidines and heterocycles linked to fructose at position 6. Such compounds are potential inhibitors of the specific double-substrate MeSAdo/AdoHcy nucleosidase enzyme, governing the hydrolysis of MeSAdo and AdoHcy nucleosides. In the parasite, the hydrolysis leads to 5-methylthioribose and S-ribosylhomocysteine as reaction products.