TowardsAlmiramides analogues as potential chemotherapeutics agents

Kinetoplastid diseases, as sleeping sickness, leishmaniasis and Chagas disease, are called neglected diseases. The chemotherapies suffer from several limitations such as cost, high toxicity, difficulty in administration and spread of drug resistance. Linington’s group describes a new class of leishmaniasis lead compounds, Almiramides C and D, from organic extract of the marine cyanobacterium Lyngbya majuscule. These almiramides, showed in vitro activity against Leishmania donovani. As part of our group search for compounds as candidates for antiparasitic drugs employing molecular simplification of natural products, we are interested in the synthesis of linear lipopeptides as almiramides analogues.
In this work, we present the strategy to prepare dipeptides as building blocks employing amide bond formation. We studied some reaction conditions to prepare methylated amides. Analogues synthetized will be submitted to study biological activities against L. infantum (amastigote form), T. b. brucei and we will study cytotoxicity in murine macrophages (J774 cell line).