TY - JOUR
T1 - Synthesis and Biological Evaluation of Amphotericin B Formulations Based on Organic Salts and Ionic Liquids against Leishmania infantum
AU - Ferraz, Ricardo
AU - Santarém, Nuno
AU - Santos, Andreia F. M.
AU - Jacinto, Manuel L.
AU - Cordeiro-da-Silva, Anabela
AU - Prudêncio, Cristina
AU - Noronha, João Paulo
AU - Branco, Luis C.
AU - Petrovski, Zeljko
N1 - Funding text
This research was funded by the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was also supported by the Associate Laboratory for Green Chemistry LAQV financed by national funds from FCT/MCTES (UIDB/50006/2020, UIDP/50006/2020 and LA/P/0008/2020). The authors also thank Fundação para a Ciência e Tecnologia for the projects PTDC/EAM-AMB/2023/2021, PTDC/QUI-QOR/32406/2017 and PTDC/BTM-SAL/29786/2017. N.S. was supported by PTDC/SAU-PAR/31013/2017. A.F.M.S and Ž.P. also acknowledge FCT-MCTES for the PhD Grant (SFRH/BD/132551/2017) and for the Norma Transitória DL 57/2016 Program contract, respectively. The NMR spectrometers are part of The National NMR Facility, supported by FCT (ROTEIRO/0031/2013 - PINFRA/22161/2016) (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC).
PY - 2022/12/19
Y1 - 2022/12/19
N2 - 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.
AB - 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.
KW - active pharmaceutical ingredients
KW - amphotericin B
KW - Leishmania infantum
KW - leishmaniasis
KW - organic salts and ionic liquids
U2 - 10.3390/antibiotics11121841
DO - 10.3390/antibiotics11121841
M3 - Article
C2 - 36551498
SN - 2079-6382
VL - 11
JO - Antibiotics
JF - Antibiotics
IS - 12
M1 - 1841
ER -