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1-Dodecyl-2-methylpyridinium bromide ([C12-2-Pic][Br]) and 1-hexadecyl-2-methylpyridinium bromide ([C16-2-Pic][Br]) are two ionic liquid crystals presenting thermotropic smectic phases above 80 °C. Aiming to take advantage of the liquid crystalline properties at lower temperatures, lyotropic aqueous systems were prepared from these two organic salts. Both systems were characterized by polarized optical microscopy (POM), X-ray powder diffraction (XRD), and fast field cycling nuclear magnetic resonance (FFC-NMR) relaxometry to assess their texture, phase structure, and molecular dynamics, respectively. The mesomorphic behavior was induced at room temperature. Moreover, the lyotropic [C12-2-Pic][Br]aq revealed a smectic phase with higher separation between layers, different from the lamellar phases found in the thermotropic system (S1 and SA), which is thermally stable up to 50 °C. Furthermore, the surfactant nature of the ionic liquids diluted solutions investigated in this work allowed the formation of foams. It was found that the precursor solutions of the lyotropic dilutions with the longest alkyl chain ([C16-2-Pic][Br]aq) originated liquid foams with more stable structures than those of [C12-2-Pic][Br]aq.
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The unique physicochemical properties of ionic liquids (ILs) attracted interest in their application as lubricants of micro/nano-electromechanical systems. This work evaluates the feasibility of using the protic ionic liquids [4-picH][HSO4], [4-picH][CH3SO3], [MIMH][HSO4], and [MIMH][CH3SO3] and the aprotic ILs [C6mim][HSO4] and [C6mim][CH3SO3] as additives to model lubricant poly(ethylene glycol) (PEG200) to lubricate silicon surfaces. Additives based on the cation [4-picH]+ exhibited the best tribological performance, with the optimal value for 2% [4-picH][HSO4] in PEG200 (w/w). Molecular dynamics (MD) simulations of the first stages of adsorption of the ILs at the glass surface were performed to portray the molecular behavior of the ILs added to PEG200 and their interaction with the silica substrate. For the pure ILs at the solid substrates, the MD results indicated that weak specific interactions of the cation with the glass interface are lost to accommodate the larger anion in the first contact layer. For the PEG200 + 2% [4-picH][HSO4] system, the formation of a more compact protective film adsorbed at the glass surface is revealed by a larger trans population of the dihedral angle -O(R)-C-C-O(R)- in PEG200, in comparison to the same distribution for the pure model lubricant. Our findings suggest that the enhanced lubrication performance of PEG200 with [4-picH][HSO4] arises from synergistic interactions between the protic IL and PEG200 at the adsorbed layer.
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Marine sponges are highly efficient in removing organic pollutants and their cultivation, adjacent to fish farms, is increasingly considered as a strategy for improving seawater quality. Moreover, these invertebrates produce a plethora of bioactive metabolites, which could translate into an extra profit for the aquaculture sector. Here, we investigated the chemical profile and bioactivity of two Mediterranean species (i.e., Agelas oroides and Sarcotragus foetidus) and we assessed whether cultivated sponges differed substantially from their wild counterparts. Metabolomic analysis of crude sponge extracts revealed species-specific chemical patterns, with A. oroides and S. foetidus dominated by alkaloids and lipids, respectively. More importantly, farmed and wild explants of each species demonstrated similar chemical fingerprints, with the majority of the metabolites showing modest differences on a sponge mass-normalized basis. Furthermore, farmed sponge extracts presented similar or slightly lower antibacterial activity against methicillin-resistant Staphylococcus aureus, compared to the extracts resulting from wild sponges. Anticancer assays against human colorectal carcinoma cells (HCT-116) revealed marginally active extracts from both wild and farmed S. foetidus populations. Our study highlights that, besides mitigating organic pollution in fish aquaculture, sponge farming can serve as a valuable resource of biomolecules, with promising potential in pharmaceutical and biomedical applications.
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Agelas , Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Poríferos , Animales , Humanos , Poríferos/química , Agelas/química , Staphylococcus aureus Resistente a Meticilina/metabolismo , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/metabolismoRESUMEN
The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts, and two other, different cation families, were combined with Gadolinium(III) and Terbium(III) anions. Synthetic methodologies were previously optimized, and all organic salts were obtained as solids with melting temperatures higher than 100 °C. The magnetic moments obtained for the Gd(III) salts were, as expected, smaller than those obtained for the Tb(III)-based compounds. The values for Gd(III) and Tb(III) magnetic salts are in the range of 6.55-7.30 MB and 8.22-9.34 MB, respectively. It is important to note a correlation between the magnetic moments obtained for lanthanides, and the structural features of the cation. The cytotoxicity of lanthanide-based salts was also evaluated using 3T3, 293T, Caco2, and HepG2 cells, and it was revealed that most of the prepared compounds are not toxic.
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Elementos de la Serie de los Lantanoides , Humanos , Elementos de la Serie de los Lantanoides/farmacología , Elementos de la Serie de los Lantanoides/química , Sales (Química) , Células CACO-2 , Aniones , CationesRESUMEN
The combination of active pharmaceutical ingredients in the form of ionic liquids or organic salts (API-OSILs) with mesoporous silica nanoparticles (MSNs) as drug carriers can provide a useful tool in enhancing the capabilities of current antibiotics, especially against resistant strains of bacteria. In this publication, the preparation of a set of three nanomaterials based on the modification of a MSN surface with cholinium ([MSN-Chol][Cip]), 1-methylimidazolium ([MSN-1-MiM][Cip]) and 3-picolinium ([MSN-3-Pic][Cip]) ionic liquids coupled with anionic ciprofloxacin have been reported. All ionic liquids and functionalized nanomaterials were prepared through sustainable protocols, using microwave-assisted heating as an alternative to conventional methods. All materials were characterized through FTIR, solution 1H NMR, elemental analysis, XRD and N2 adsorption at 77 K. The prepared materials showed no in vitro cytotoxicity in fibroblasts viability assays. The minimum inhibitory concentration (MIC) for all materials was tested against Gram-negative K. pneumoniae and Gram-positive Enterococcus spp., both with resistant and sensitive strains. All sets of nanomaterials containing the anionic antibiotic outperformed free ciprofloxacin against resistant and sensitive forms of K. pneumoniae, with the prominent case of [MSN-Chol][Cip] suggesting a tenfold decrease in the MIC against sensitive strains. Against resistant K. pneumoniae, a five-fold decrease in the MIC was observed for all sets of nanomaterials compared with neutral ciprofloxacin. Against Enterococcus spp., only [MSN-1-MiM][Cip] was able to demonstrate a slight improvement over the free antibiotic.
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Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM] + cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.
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Líquidos Iónicos , Tiroxina , Tiroxina/síntesis química , Tiroxina/farmacocinética , Tiroxina/toxicidad , Disponibilidad Biológica , Solubilidad , Líquidos Iónicos/síntesis química , Líquidos Iónicos/farmacocinética , Líquidos Iónicos/toxicidad , Células L , Animales , Ratones , PermeabilidadRESUMEN
Five Covalent Organic Frameworks (COFs) were synthesized and applied to Dye-Sensitized Solar Cells (DSSCs) as dyes and additives. These porous nanomaterials are based on cheap, abundant commercially available ionic dyes (thionin acetate RIO-43, Bismarck brown Y RIO-55 and pararosaniline hydrochloride RIO-70), and antibiotics (dapsone RIO-60) are used as building blocks. The reticular innovative organic framework RIO-60 is the most promising dye for DSSCs. It possesses a short-circuit current density (Jsc) of 1.00 mA/cm2, an open-circuit voltage (Voc) of 329 mV, a fill factor (FF) of 0.59, and a cell efficiency (η) of 0.19%. These values are higher than those previously reported for COFs in similar devices. This first approach using the RIO family provides a good perspective on its application in DSSCs as a dye or photoanode dye enhancer, helping to increase the cell's lifespan.
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The motivation for this work was to develop new protic ionic liquids (PILs) as additives for the lubrication of micro and nanoelectromechanical systems (MEMS and NEMS). Ten PILs based on the combination of methylimidazolium ([MIMH]), 4-picolinium ([4-picH]), pyridinium ([PyrH]), 1,8-diazabicyclo[5.4.0]-undec-7-ene-8-ium ([DBUH]) and tetramethylguanidinium ([TMGH]) cations with hydrogen sulfate([HSO4]) and mesylate ([MeSO3]) anions were tested as additives in polyethylene glycol (PEG200) to lubricate steel/silicon and silicon/silicon contacts. The best additive was [4-picH][HSO4], which adsorbed strongly on the Si surface, leading to a protective film that reduced wear by up to 15 times compared to PEG200.
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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.
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The use of ionic liquid and organic salts as additives for electrolyte systems in dye-sensitized solar cells have been widely described in recent years. The tunability of their physical-chemical properties according to the cation-anion selection contributes toward their high efficiencies. For this purpose, several iodide-based organic salts including imidazolium, picolinium, guanidinium and alkylammonium cations were tested using acetonitrile/valeronitrile electrolytes and their photovoltaic parameters were compared. A best efficiency of 4.48% (4.15% for the reference) was found for 1-ethyl-2,3-dimethylimidazolium iodide ([C2DMIM]I) containing electrolyte, reaffirming the effectiveness of these additives. 4-tertbutylpyridine was included into the formulation to further improve the performance while determining which iodide salts demonstrate the highest synergy with this additive. [C2DMIM]I once again proved to be the superior additive, achieving an efficiency of 6.48% (6% for the reference). Electrochemical impedance spectroscopy was employed to elucidate the effects of the various additives, demonstrating the relevance of the counter electrode resistance on device performance. Finally, several computational descriptors for the cationic structures were calculated and correlated with the photovoltaic and resistance parameters, showing that properties related to polarity, namely relative positive charge, molecular polarizability and partition coefficient are in good agreement with the counter-electrode resistance.
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The development of novel pharmaceutical tools to efficiently tackle tuberculosis is the order of the day due to the rapid development of resistant strains of Mycobacterium tuberculosis. Herein, we report novel potential formulations of a repurposed drug, the antimalarial mefloquine (MFL), which was combined with organic anions as chemical adjuvants. Eight mefloquine organic salts were obtained by ion metathesis reaction between mefloquine hydrochloride ([MFLH][Cl]) and several organic acid sodium salts in high yields. One of the salts, mefloquine mesylate ([MFLH][MsO]), presented increased water solubility in comparison with [MFLH][Cl]. Moreover, all salts with the exception of mefloquine docusate ([MFLH][AOT]) showed improved permeability and diffusion through synthetic membranes. Finally, in vitro activity studies against Mycobacterium tuberculosis revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], particularly mefloquine camphorsulfonates ([MFLH][(1R)-CSA], [MFLH][(1S)-CSA]) and mefloquine HEPES ([MFLH][HEPES]).
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Antimaláricos , Mycobacterium tuberculosis , Antimaláricos/farmacología , HEPES , Mefloquina/farmacología , Permeabilidad , Sales (Química) , SolubilidadRESUMEN
The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.
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The generalized use of antibiotics in veterinary medicine may cause the development of antibiotic resistance, namely, in farmed fish, and subsequently, transmission of such resistance to humans. To overcome this serious problem, it is necessary to improve the efficiency of antibiotic removal processes from water, and a route for attaining that goal is the use of hydrophobic ionic liquids. LC-MS/MS is an analytical technique with proven utility for pharmaceutical identification and quantification. A methodology for the identification and quantification of five antibiotics, namely ampicillin, amoxicillin, chloramphenicol, enrofloxacin and oxytetracycline, from four families, namely ß-lactams, phenicols, quinolones and tetracyclines, was developed and validated using one SPE extraction and clean-up step for detection analysis by LC-MS/MS. The selected linear range for each analyte is as follows: 5-200 ng mL-1 for ampicillin; 0.1-200 ng mL-1 for amoxicillin and chloramphenicol; and 1-200 ng mL-1 for enrofloxacin and oxytetracycline, respectively. The limits of detection for each target analyte vary between 0.01 ng mL-1 and 0.81 ng mL-1, and the limits of quantification for each target analyte vary between 0.1 ng mL-1 and 5 ng mL-1 for the five antibiotics under study. The extraction recovery value range is between 89.91% and 100.33%. The validation proved that the developed methodology is suitable for the identification and quantification of ampicillin, amoxicillin, chloramphenicol, enrofloxacin and oxytetracycline. After validation, this new assay was successfully applied to a liquid-liquid extraction process using a hydrophobic ionic liquid.
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Antibacterianos , Agua , Animales , Antibacterianos/análisis , Cromatografía Liquida , Humanos , Espectrometría de Masas en Tándem/métodos , Agua/química , beta-Lactamas/análisisRESUMEN
Bisphosphonates are a class of drugs widely used for the treatment of several pathologies associated with increased bone resorption. Although displaying low oral bioavailability, these drugs have the ability to accumulate in bone matrix, where the biological effects are exerted. In the present work, four mono- and dianionic Etidronate-based Organic Salts and Ionic Liquids (Eti-OSILs) were developed by combination of this drug with the superbases 1,1,3,3-tetramethylguanidine (TMG) and 1,5-diazabicyclo(4.3.0)non-5-ene (DBN) as cations, aiming to improve not only the physicochemical properties of this seminal bisphosphonate, but also its efficacy in the modulation of cellular behavior, particularly on human osteoclasts and osteoblasts. It was observed that some of the developed compounds, in particular the dianionic ones, presented very high water solubility and diminished or absent polymorphism. Also, several of them appeared to be more cytotoxic against human breast and osteosarcoma cancer cell lines while retaining low toxicity to normal cells. Regarding bone cells, a promotion of an anabolic state was observed for all Eti-OSILs, primarily for the dianionic ones, which leads to an inhibition of osteoclastogenesis and an increase in osteoblastogenesis. The observed effects resulted from differential modulation of intracellular signaling pathways by the Eti-OSILs in comparison with Etidronate. Hence, these results pave the way for the development of more efficient and bioavailable ionic formulations of bisphosphonates aiming to effectively modulate bone metabolism, particularly in the case of increased bone resorption.
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Ácido Etidrónico , Líquidos Iónicos , Difosfonatos/farmacología , Humanos , Osteoclastos , Sales (Química)RESUMEN
Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.
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Humanos , Adulto , Trastorno Depresivo Mayor/terapia , Estimulación Transcraneal de Corriente Directa , Encéfalo , Ensayos Clínicos Controlados Aleatorios como Asunto , Metaanálisis como Asunto , Depresión , Fenómenos MagnéticosRESUMEN
Deep eutectic solvents (DES), a new class of alternative solvents, have recently been used in the pre-treatment of lignocellulosic biomass. Due to the ability to dissolve phenolic compounds, they have been efficiently applied as delignification agents. However, to extend DES application to bioprocesses, such as Anaerobic Digestion (AD), their toxicity to microbial consortia must be evaluated. In this work, an effective delignifying DES, composed of choline chloride (ChCl) and oxalic acid (OA) (1:1) was prepared and its effect evaluated, for the first time, in biogas production. Results show that the presence of DES had both beneficial and detrimental effects on the anaerobic consortium, depending on its concentration. In the concentration range of 0.3-12.5 g/L, the presence of DES led to a lag-phase of 1 to 8 d as the DES concentration increased. However, after the lag-phase has been surpassed, DES up to a concentration of 12.5 g/L improved the biogas production, reaching an accumulated biogas volume three times higher than the control assay for the concentration of 12.5 g/L. For the highest DES concentrations (19.8-78.1 g/L), the biogas production was inhibited. The assays performed with DES components alone have indicated that OA at 3.2 g/L was the main responsible for the inhibition of biogas production (50% less biogas produced than the control). ChCl at 4.9 g/L has not presented a lag-phase and produced an accumulated biogas volume like the control assay (1200 mL for 30 d incubation). This work points out that ChCl:OA DES may be used in the delignification of biomass further submitted to AD, provided the inhibitory concentrations of OA are not achieved.
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Biocombustibles , Colina , Biomasa , Ácido Oxálico , SolventesRESUMEN
Several organic salts based on the combination of two different choline derivative cations and MnCl3-, GdCl4- and TbCl4- as anions were immobilized in mesoporous silica nanoparticles (MSNs) by a two-step synthetic method. Firstly, MSNs were functionalized with choline derivative cations with chloride anions and then the metals were incorporated by the reaction of the chloride with the respective metal chloride salts. These nanomaterials were fully characterized by different characterization techniques such as 1H-NMR, FT-IR, elemental analysis, TEM, TGA, N2 adsorption, XRD and DLS. These characterization data were important to confirm the successful functionalization of the nanomaterials and to access their textural properties and colloidal stability. The final materials were also characterized by ICP-MS that indicated the metal contents. The cytotoxicity profile was evaluated in four different cell lines (3T3, 293T, HepG2 and Caco-2), which shows some relevant differences between the metal organic salts and their immobilized analogues.
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Elementos de la Serie de los Lantanoides/química , Manganeso/química , Nanopartículas/química , Dióxido de Silicio/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Elementos de la Serie de los Lantanoides/toxicidad , Manganeso/toxicidad , Ratones , Nanopartículas/toxicidad , Nanopartículas/ultraestructura , Porosidad , Sales (Química)/química , Dióxido de Silicio/toxicidadRESUMEN
Mesoporous silica nanoparticles (MSNs) are very promising nanomaterials for treating bacterial infections when combined with pharmaceutical drugs. Herein, we report the preparation of two nanomaterials based on the immobilization of ciprofloxacin in mesoporous silica nanoparticles, either as the counter-ion of the choline derivative cation (MSN-[Ch][Cip]) or via anchoring on the surface of amino-group modified MSNs via an amide bond (MSN-Cip). Both nanomaterials were characterized by TEM, FTIR and solution 1H NMR spectroscopies, elemental analysis, XRD and N2 adsorption at 77 K in order to provide the desired structures. No cytotoxicity from the prepared mesoporous nanoparticles on 3T3 murine fibroblasts was observed. The antimicrobial activity of the nanomaterials was determined against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Klebsiella pneumoniae) bacteria and the results were promising against S. aureus. In the case of B. subtilis, both nanomaterials exhibited higher antimicrobial activity than the precursor [Ch][Cip], and in the case of K. pneumoniae they exhibited higher activity than neutral ciprofloxacin.
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Aspergillus species are the primary cause of invasive aspergillosis, which afflicts hundreds of thousands of patients yearly, with high mortality rates. Amphotericin B is considered the gold standard in antifungal drug therapy, due to its broad-spectrum activity and rarely reported resistance. However, low solubility and permeability, as well as considerable toxicity, challenge its administration. Lipid formulations of amphotericin B have been used to promote its slow release and diminish toxicity, but these are expensive and adverse health effects of their prolonged use have been reported. In the past decades, great interest emerged on converting biologically active molecules into an ionic liquid form to overcome limitations such as low solubility or polymorphisms. In this study, we evaluated the biological activity of novel ionic liquid formulations where the cholinium, cetylpyridinium or trihexyltetradecylphosphonium cations were combined with an anionic form of amphotericin B. We observed that two formulations increased the antifungal activity of the drug, while maintaining its mode of action. Molecular dynamics simulations showed that higher biological activity was due to increased interaction of the ionic liquid with the fungal membrane ergosterol compared with amphotericin B alone. Increased cytotoxicity could also be observed, probably due to greater interaction of the cation with cholesterol, the main sterol in animal cells. Importantly, one formulation also displayed antibacterial activity (dual functionality), likely preserved from the cation. Collectively, the data set ground for the guided development of ionic liquid formulations that could improve the administration, efficacy and safety of antifungal drugs or even the exploitation of their dual functionality.
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Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.