Synthesis and biological evaluation of Amphotericin B formulations based on organic salts and ionic liquids against Leishmania infantum

• Published in: Antibiotics (Basel) Vol. 11(12); no. 12; pp. 1 - 12
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 19.12.2022; MDPI AG
• Subjects: Active pharmaceutical ingredients; Ammonium; Amphotericin B; Antiprotozoal activity; Biological activity; Cations; Drug delivery; Drug delivery systems; Formulations; Ionic liquids; Ions; Leishmania infantum; Leishmaniasis; Neutralization; Optical properties; Optical rotation; Organic salts; Organic salts and ionic liquids; Parasitic diseases; Permeability; Pharmaceutical industry; Promastigotes; Pyridinium; Reagents; Salts; Solvents; Synergism; Toxicity; Tropical diseases; Vector-borne diseases; Leishmania infantum; amphotericin B; leishmaniasis; active pharmaceutical ingredients; organic salts and ionic liquids
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics11121841

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.