Structure and metabolism of the VSG monolayer

Abstract

The ability of drugs to show therapeutic activity in vitro can be affected by their hydrophobicity (log P). We recently reported the presence of antiparasitic activity within a group of glutathione diesters [I], against Trypanosoma brucei, Leishmania donovanz and Trypanosoma muzi. In this study we show the dependence of antiparasitic activity (ED50) vs log P and indicate an optimum value for the effectiveness of peptidyl drugs against strains of Tb. brucei. Whilst hydrophobicity is a principal component for activity, steric factors also contribute to the observed pattern with these prodrugs. The mechanism of anti-parasitic action of these glutathione prodrugs will be presented and the protein targets qualitatively identified by sensors studies [2].