Author(s): Ferraz, Ricardo ; Santarém, Nuno ; Santos, Andreia F. M. ; Jacinto, Manuel L. ; Cordeiro-da-Silva, Anabela ; Prudêncio, Cristina ; Noronha, João Paulo ; Branco, Luis C. ; Petrovski, Željko
Date: 2022
Persistent ID: http://hdl.handle.net/10400.22/22069
Origin: Repositório Científico do Instituto Politécnico do Porto
Subject(s): Organic salts and ionic liquids; Amphotericin B; Active pharmaceutical ingredients; Leishmania infantum; Leishmaniasis
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]D25) 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 [P6,6,6,14][AmB] as the most promising formulation. Possible synergism in the antiprotozoal activity was also evaluated for [P6,6,6,14][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.
