Synthesis and Biological Evaluation of Amphotericin B Formulations Based on Organic Salts and Ionic Liquids against Leishmania infantum

Nowadays, organic salts and ionic liquids (OSILs) containing active pharmaceutical ingredients (APIs) are being explored as drug delivery systems in modern therapies (OSILs-API). In that sense, this work is focused on the development of novel OSILs-API based on amphotericin B through an innovative procedure and the evaluation of the respective biological activity against Leishmania infantum. Several ammonium, methylimidazolium, pyridinium and phosphonium organic cations combined with amphotericin B as anion were synthesized in moderate to high yields and high purities by the water-reduced buffer neutralization method. All prepared compounds were characterized to confirm the desired chemical structure and the specific optical rotation ([α](D)(25)) was also determined. The biological assays performed on L. infantum promastigotes showed increased activity against this parasitic disease when compared with the starting chloride forms and amphotericin B alone, highlighting [P(6,6,6,14)][AmB] as the most promising formulation. Possible synergism in the antiprotozoal activity was also evaluated for [P(6,6,6,14)][AmB], since it was proven to be the compound with the highest toxicity. This work reported a simple synthetic method, which can be applied to prepare other organic salts based on molecules containing fragile chemical groups, demonstrating the potential of these OSILs-AmB as possible agents against leishmaniasis.