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1.
AAPS PharmSciTech ; 25(7): 210, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39242368

RESUMO

Torsemide is a long acting pyridine sulfonylurea diuretic. Torsemide hydrochloride is widely used now, there are only a few organic acid salts reported. Cocrystallization with organic acids is an effective way to improve its solubility. Here, we reported maleate and phthalate of torsemide, in which the organic acid lost a proton transferring to the pyridine of torsemide, and torsemide interacted with organic acid through N+ - H⋯O- hydrogen bond to form salts crystal. Surprisingly, maleate showed a clear "spring" pattern in apparent solubility, whereas phthalate had a "spring-parachute" effect. Both crystalline salts kept a higher solubility than torsemide without falling. The "spring-parachute" effect of crystalline salts promoted rapid dissolution of torsemide and kept a high concentration, thereby increasing its bioavailability.


Assuntos
Cristalização , Sais , Solubilidade , Torasemida , Torasemida/química , Cristalização/métodos , Sais/química , Ligação de Hidrogênio , Diuréticos/química , Maleatos/química , Disponibilidade Biológica
2.
Biotechnol J ; 19(9): e2400394, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39246125

RESUMO

The development of liquid biopsy as a minimally invasive technique for tumor profiling has created a need for efficient biomarker extraction systems from body fluids. The analysis of circulating cell-free DNA (cfDNA) is especially promising, but the low amounts and high fragmentation of cfDNA found in plasma pose challenges to its isolation. While the potential of aqueous two-phase systems (ATPS) for the extraction and purification of various biomolecules has already been successfully established, there is limited literature on the applicability of these findings to short cfDNA-like fragments. This study presents the partitioning behavior of a 160 bp DNA fragment in polyethylene glycol (PEG)/salt ATPS at pH 7.4. The effect of PEG molecular weight, tie-line length, neutral salt additives, and phase volume ratio is evaluated to maximize DNA recovery. Selected ATPS containing a synthetic plasma solution spiked with human serum albumin and immunoglobulin G are tested to determine the separation of DNA fragments from the main plasma protein fraction. By adding 1.5% (w/w) NaCl to a 17.7% (w/w) PEG 400/17.3% (w/w) phosphate ATPS, 88% DNA recovery was achieved in the salt-rich bottom phase while over 99% of the protein was removed.


Assuntos
Polietilenoglicóis , Polietilenoglicóis/química , Humanos , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/química , Ácidos Nucleicos Livres/isolamento & purificação , Cloreto de Sódio/química , DNA/química , DNA/isolamento & purificação , Polímeros/química , Biópsia Líquida/métodos , Sais/química
3.
Mar Pollut Bull ; 207: 116905, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39241366

RESUMO

Seawater desalination is one of the most feasible technologies for producing fresh water to address the water scarcity scenario worldwide. However, environmental concerns about the potential impact of brine discharge on marine ecosystems hinder or delay the development of desalination projects. In addition, scientific knowledge is lacking about the impact of brine discharges on the South America Pacific coast where desalination, is being developed. This paper presents the first monitoring results of brine discharge influence areas from seawater reverse osmosis desalination plants (SWRO) on the South America Pacific coast, using Chile as case study. Our results indicate that the combination of favorable oceanographic conditions and diffusers, results in the rapid dilution of brine discharge on coastal ecosystems; showing a faster dilution than other SWRO plants in other regions, such as Mediterranean or Arabian Gulf, with similar production characteristics. Also, the increase in salinity over the natural salinity in the brine-discharge-affected area was <5 % in a radius of <100 m from the discharge points. Further, according to the published literature and on our monitoring results, we propose a number of considerations (environmental regulation, best scientifically tested measures, environmental requirements) to achieve a long-term sustainable desalination operation.


Assuntos
Salinidade , Água do Mar , Chile , Monitoramento Ambiental/métodos , Sais/análise , Osmose , Purificação da Água/métodos , Oceano Pacífico , Ecossistema
4.
Eur J Med Chem ; 277: 116775, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39153333

RESUMO

This study reports a new series of 1,10-phenanthroline-substituted imidazolium salts (1a-f), examining their design, synthesis, structure and anticancer activities. The structures of these salts (1a-f) were characterized using 1H, 13C NMR, elemental analysis, mass spectrometry and Fourier transform infrared (FT-IR) spectroscopies. The salts' cytotoxic activities were tested against cancer cell lines, specifically MCF-7, MDA-MB-231 and non-tumorigenic MCF-10A mammary cells. The study compared the impact of aliphatic and benzylic groups in the salts' structure on their anticancer activity. Screening results revealed that compound 1c, in particular, showed promising inhibitory activity against the growth of MDA-MB-231 breast cancer cells, with an IC50 value of 12.8 ± 1.2 µM, indicating its potential as a chemotherapeutic agent. Cell apoptosis analysis demonstrated a tendency for compound 1c to induce early apoptosis in breast cancer cells. The stability/aquation of compound 1c was investigated using 1H NMR spectroscopy and its binding modes with DNA were explored via UV-Vis spectroscopy. Additionally, the study investigated the interaction residues and docking scores of compound 1c and the reference drug doxorubicin against Bax and Bcl-2 proteins using molecular docking.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Imidazóis , Fenantrolinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imidazóis/farmacologia , Imidazóis/química , Imidazóis/síntese química , Simulação de Acoplamento Molecular , Estrutura Molecular , Fenantrolinas/química , Fenantrolinas/farmacologia , Fenantrolinas/síntese química , Sais/química , Sais/farmacologia , Sais/síntese química , Relação Estrutura-Atividade , Compostos Heterocíclicos com 3 Anéis/síntese química , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacologia
5.
Biomacromolecules ; 25(9): 6203-6215, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39153217

RESUMO

Introducing kosmotropic salts enhances protein stability and reduces solubility by withdrawing water from the protein surface, leading to 'salting out', a phenomenon we have mimicked in supramolecular polymers (SPs). Under the guidance of Ag+, folic acid (FA) self-assembled in water through slipped-stacking and hydrophobic interactions into elongated, robust one-dimensional SPs, resulting in thermo-stable supergels. The SPs exhibited temperature and dilution tolerance, attributed to the stability of the FA-Ag+ complex and its hydrophobic stacking. Importantly, FA-Ag+ SP's stability has been augmented by the kosmotropic anions, such as SO42-, strengthening hydrophobic interactions in the SP, evident from the enhanced J-band, causing improvement of gel's mechanical property. Interestingly, higher kosmotrope concentrations caused a significant decrease in SP's solubility, leading to precipitation of the reinforced SPs─a 'salting out' effect. Conversely, chaotropes like ClO4- slightly destabilized hydrophobic stacking and promoted an extended conformation of individual SP chain with enhanced solubility, resembling a 'salting in' effect.


Assuntos
Ânions , Ácido Fólico , Interações Hidrofóbicas e Hidrofílicas , Polímeros , Prata , Solubilidade , Ácido Fólico/química , Ânions/química , Polímeros/química , Prata/química , Sais/química
6.
Int J Biol Macromol ; 277(Pt 3): 134291, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39089542

RESUMO

Tuftelin Interacting Protein 11 (TFIP11) was identified as a critical human spliceosome assembly regulator, interacting with multiple proteins and localising in membrane-less organelles. However, a lack of structural information on TFIP11 limits the rationalisation of its biological role. TFIP11 is predicted as an intrinsically disordered protein (IDP), and more specifically concerning its N-terminal (N-TER) region. IDPs lack a defined tertiary structure, existing as a dynamic conformational ensemble, favouring protein-protein and protein-RNA interactions. IDPs are involved in liquid-liquid phase separation (LLPS), driving the formation of subnuclear compartments. Combining disorder prediction, molecular dynamics, and spectroscopy methods, this contribution shows the first evidence TFIP11 N-TER is a polyampholytic IDP, exhibiting a structural duality with the coexistence of ordered and disordered assemblies, depending on the ionic strength. Increasing the salt concentration enhances the protein conformational flexibility, presenting a more globule-like shape, and a fuzzier unstructured arrangement that could favour LLPS and protein-RNA interaction. The most charged and hydrophilic regions are the most impacted, including the G-Patch domain essential to TFIP11 function. This study gives a better understanding of the salt-dependent conformational behaviour of the N-TER TFIP11, supporting the hypothesis of the formation of different types of protein assembly, in line with its multiple biological roles.


Assuntos
Proteínas Intrinsicamente Desordenadas , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas Intrinsicamente Desordenadas/genética , Humanos , Conformação Proteica , Simulação de Dinâmica Molecular , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Fatores de Processamento de RNA/química , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/genética , Sais/química , Domínios Proteicos
7.
J Environ Manage ; 368: 122207, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39180824

RESUMO

Mountain salts produced from the highland region in NE Sarawak have a market value and also provide basic income to the communities. During the salt-making process, microplastics (MPs) may enter into commercial table salts from various sources, which has not been explored yet. Hence, the current research investigates the presence of MPs in the rock salts produced from the highland saline water in two different locations (L1 and L2) in NE Sarawak. Among the brine water and rock salt samples analysed, the highest concentrations of MPs were detected from the salt samples. It has been revealed that both the water and salt samples have the highest concentration of MPs occurring within the size range of 1-1000 µm. Transparent MPs are the most common colour observed in both salt and water samples, followed by white, blue, red, and black. The most prevalent shapes of MPs are fibers, which account for almost 47% in water samples and 87% in salt samples. Based on the ATR-FTIR study, polyethylene (PE) is the most prevalent polymer observed in salt samples, followed by polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET). In water samples, PP is the most dominating polymer, followed by PE and PS. Through SEM microphotographs, fiber-type MPs have smooth surfaces, fragment-type MPs have rough edges, and sheet-type MPs have layered surfaces. EDX analysis revealed that carbon (C) and oxygen (O) are the most abundant elements, followed by aluminium (Al) and sodium (Na) in MPs. Based on the results, it is inferred that the MPs in the rock salts are mainly sourced from the different stages of salt-making production. This preliminary study shed light on the presence and characteristics of MPs in rock salts in this region. The research outcomes could support sustainable management plans to improve the salt quality and enhance the market value.


Assuntos
Microplásticos , Sais , Microplásticos/análise , Sais/química , Sais/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental
8.
Int J Mol Sci ; 25(15)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39125837

RESUMO

In this work, the conformational behaviors of ring polyelectrolyte in tetravalent salt solutions are discussed in detail through molecular dynamics simulation. For simplification, here we have neglected the effect of the twisting interaction, although it has been well known that both bending and twisting interactions play a deterministic in the steric conformation of a semiflexible ring polymer. The salt concentration CS and the bending energy b take a decisive role in the conformation of the ring polyelectrolyte (PE). Throughout our calculations, the b varies from b = 0 (freely joint chain) to b = 120. The salt concentration CS changes in the range of 3.56 × 10-4 M ≤ CS ≤ 2.49 × 10-1 M. Upon the addition of salt, ring PE contracts at first, subsequently re-expands. More abundant conformations are observed for a semiflexible ring PE. For b = 10, the conformation of semiflexible ring PE shifts from the loop to two-racquet-head spindle, then it condenses into toroid, finally arranges into coil with the increase of CS. As b increases further, four phase transitions are observed. The latter two phase transitions are different. The semiflexible ring PE experiences transformation from toroid to two racquet head spindle, finally to loop in the latter two phase transitions. Its conformation is determined by the competition among the bending energy, cation-bridge, and entropy. Combined, our findings indicate that the conformations of semiflexible ring PE can be controlled by changing the salt concentration and chain stiffness.


Assuntos
Conformação Molecular , Simulação de Dinâmica Molecular , Polieletrólitos , Sais , Polieletrólitos/química , Sais/química , Soluções
9.
Nat Commun ; 15(1): 6909, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134527

RESUMO

Late-stage specific and selective diversifications of peptides and proteins performed at target residues under ambient conditions are recognized to be the most facile route to various and abundant conjugates. Herein, we report an orthogonal modification of cysteine residues using alkyl thianthreium salts, which proceeds with excellent chemoselectivity and compatibility under mild conditions, introducing a diverse array of functional structures. Crucially, multifaceted bioconjugation is achieved through clickable handles to incorporate structurally diverse functional molecules. This "two steps, one pot" bioconjugation method is successfully applied to label bovine serum albumin. Therefore, our technique is a versatile and powerful tool for late-stage orthogonal bioconjugation.


Assuntos
Cisteína , Peptídeos , Soroalbumina Bovina , Cisteína/química , Peptídeos/química , Soroalbumina Bovina/química , Sais/química , Química Click/métodos , Animais , Proteínas/química , Bovinos
10.
Biomater Adv ; 164: 213992, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39146605

RESUMO

Fibroin, the main structural protein of Bombyx mori silk, is known for its mechanical properties, its biocompatibility and degradation characteristics in vivo. Various studies investigate its uses as cell carrier and/or material for surgical implants. Multiple protocols have been established to isolate fibroin from silk fibers and to produce scaffolds and films from fibroin solution. There is only limited literature available on how fibroin scaffolds manufactured by different methods compare to each other in terms of performance as cell carriers. This study compares the behaviour of human adipose derived stromal cells (ADSC) seeded on fibroin scaffolds produced by (i) salt-leaching and (ii) freeze-thawing. One type of freeze-thawing scaffold (poresize â‰ª 315 µm) and three types of salt-leaching scaffolds (poresize ranging from 315 µm to 1000 µm) were used for this comparison. Measuring the DNA concentration on the seeded scaffolds as well as the seeded cells metabolic activity, we were able to determine freeze-thawed scaffolds to be superior for cell-seeding. ADSC seeded on salt-leaching scaffolds displayed a stronger downregulation of serum deprivation response gene than cells seeded on freeze-thaw scaffolds. In sum, our findings show that salt-leaching scaffolds offering different pore sizes differed much less among each other than salt-leaching from freeze-thawing scaffolds in terms of cell accommodation. Our work underlines the importance of physicochemical scaffold properties directly linked to different manufacturing methods and their influence on the cell seeding capacity of silk fibroin based carriers.


Assuntos
Tecido Adiposo , Fibroínas , Congelamento , Células Estromais , Alicerces Teciduais , Fibroínas/química , Alicerces Teciduais/química , Humanos , Tecido Adiposo/citologia , Células Estromais/citologia , Células Estromais/metabolismo , Células Cultivadas , Animais , Bombyx , Engenharia Tecidual/métodos , Sais/química
11.
Environ Sci Pollut Res Int ; 31(39): 52523-52539, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39153064

RESUMO

Solvent extraction of lithium from brine with a high Mg/Li ratio was investigated. Tributyl phosphate (TBP), ferric chloride (FeCl3), and kerosene were used as the extractant, co-extractant, and diluent, respectively. The mechanism of the extraction process was studied by LC-MS, UV-VIS, and FT-IR analyses. Effects of organic to aqueous phase volume ratio (O/A) on the extraction efficiency and separation factor were optimized. The effects of major parameters including Fe/Li molar ratio, hydrochloric acid concentration, and TBP volume percent as well as their interactions on the lithium extraction efficiency were evaluated using central composite design. These major parameters represent interactions within their selected ranges. While the lithium extraction efficiency as the response value in the experimental design showed the most sensitivity to the acid concentration, the separation factors were more affected by alteration in the TBP volume percent with the fixed optimum values of the other major parameters. The highest one-stage extraction efficiency of 76.3% and Li/Mg separation factor of 304 were obtained at the optimum conditions of Fe/Li = 2.99, HCl = 0.01 M, and TBP = 55%. The Mg/Li mass ratio could be significantly reduced from 192 in the feed to 1.5 in the stripping solution. Based on the findings, a schematic diagram of the process including extraction, stripping, and saponification steps was proposed.


Assuntos
Lítio , Magnésio , Solventes , Lítio/química , Solventes/química , Magnésio/química , Sais/química
12.
Mol Pharm ; 21(9): 4634-4647, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39141824

RESUMO

This study is focused on the utilization of naturally occurring salicylic acid and nicotinamide (vitamin B3) in the development of novel sustainable Active Pharmaceutical Ingredients (APIs) with significant potential for treating acne vulgaris. The study highlights how the chemical structure of the cation significantly influences surface activity, lipophilicity, and solubility in aqueous media. Furthermore, the new ionic forms of APIs, the synthesis of which was assessed with Green Chemistry metrics, exhibited very good antibacterial properties against common pathogens that contribute to the development of acne, resulting in remarkable enhancement of biological activity ranging from 200 to as much as 2000 times when compared to salicylic acid alone. The molecular docking studies also revealed the excellent anti-inflammatory activity of N-alkylnicotinamide salicylates comparable to commonly used drugs (indomethacin, ibuprofen, and acetylsalicylic acid) and were even characterized by better IC50 values than common anti-inflammatory drugs in some cases. The derivative, featuring a decyl substituent in the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water solubility and improved wettability on hydrophobic surfaces, marking it as particularly promising. To investigate the impact of the APIs on the biosphere, the EC50 parameter was determined against a model representative of crustaceans─Artemia franciscana. The majority of compounds (with the exception of the salt containing the dodecyl substituent) could be classified as "Relatively Harmless" or "Practically Nontoxic", indicating their potential low environmental impact, which is essential in the context of modern drug development.


Assuntos
Acne Vulgar , Antibacterianos , Simulação de Acoplamento Molecular , Niacinamida , Acne Vulgar/tratamento farmacológico , Niacinamida/química , Niacinamida/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Solubilidade , Salicilatos/química , Salicilatos/farmacologia , Testes de Sensibilidade Microbiana , Sais/química , Propionibacteriaceae/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ânions/química , Ácido Salicílico/química , Ácido Salicílico/farmacologia
13.
Int J Biol Macromol ; 277(Pt 4): 134353, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39089559

RESUMO

The work was aimed at evaluating the adsorptive properties of waste newspaper (WN) activated carbons chemically produced using sodium salts for methylene blue (MB) and congo red (CR) removal. The activated carbons, designated as AC1, AC2, AC3 and AC4 were prepared through impregnation with NaH2PO4, Na2CO3, NaCl and NaOH, respectively and activation at 500 °C for 1 h. The activated carbons were characterized for surface chemistry, thermal stability, specific area, morphology and composition. The AC1 with a surface area of 917 m2/g exhibits a greater MB capacity of 651 mg/g. Meanwhile, a greater CR capacity was recorded by AC2 at 299 mg/g. The pseudo-second order model fitted well with the kinetic data, while the equilibrium data could be described by Langmuir model. The thermodynamic parameters, i.e.., positive ΔH°, negative ΔG° and positive ΔS° suggest that the adsorption of dyes is endothermic, spontaneous and feasible at high solution temperature. To conclude, WN is a potential cellulose source for producing activated carbon, while NaH2PO4 activation could be employed to convert WN into activated carbon for effective dye wastewater treatment.


Assuntos
Celulose , Carvão Vegetal , Vermelho Congo , Azul de Metileno , Azul de Metileno/química , Celulose/química , Vermelho Congo/química , Adsorção , Carvão Vegetal/química , Cinética , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Papel , Purificação da Água/métodos , Termodinâmica , Sais/química , Temperatura
14.
Water Res ; 265: 122261, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39167970

RESUMO

Phosphorus (P) recovered from sludge-incinerated ash (SIA) could be applied to synthesize highly added-value products (FePO4 and LiFePO4) with in situ Fe in SIA. Indeed, LiFePO4 is a future of rechargeable batteries, which makes lithium (Li) highly needed. Alternatively, Li could also be extracted from concentrated brines to face a potential crisis of Li depletion on lands. Based on H3PO4 and Fe3+ co-extracted from the acidic leachate of SIA by tributyl phosphate (TBP), FePO4 (31.2 wt% Fe, 17.6 wt% P and the molar ratio of Fe/P = 0.98) was easily formed only adjusting pH of the stripping solution to 1.6. Interestingly, the organic phase from the first-stage co-extraction process of Fe3+ and H3PO4 could be utilized for Li-extraction from salt-lake brine, based on the TBP-FeCl3-kerosene system, and a good performance (78.7%) of Li-extraction and separation factors (ß) (186.0-217.4) were obtained. Furthermore, the compounds with Li-extraction are complex, possibly LiFeCl4∙2TBP, in which Li+ could be stripped to form Li2CO3 by 4.0 M HCl (with a stripping rate up to 83%). Besides, Li2CO3 could also be obtained from desalinated brine by adsorption with manganese oxide ion sieve (HMO) and desorption with HCl. In the two cases, almost pure Li2CO3 products were obtained, up to 99.7 and 99.5 wt% Li2CO3 respectively, after further purification and concentration. Finally, recovered FePO4 and extracted Li2CO3 were synthesized for producing LiFePO4 that had a similar electrochemical property (69.5 and 77.8 mAh/g of the initial discharge capacity) to those synthesized from commercial raw materials.


Assuntos
Ferro , Lítio , Fosfatos , Esgotos , Lítio/química , Fosfatos/química , Ferro/química , Esgotos/química , Sais/química , Compostos Férricos
15.
Int J Biol Macromol ; 278(Pt 3): 134797, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39217041

RESUMO

The chemocatalystic conversion of cellulose, the main component of lignocellulosic biomass, to building-block chemicals in water under mild conditions, is an ideal but highly challenging process due to the robust crystal structure of cellulose. It is also the key to establishing a sustainable biomass-based chemical process. Here, we present a highly efficient and selective chemocatalytic hydrolysis of cellulose using ZnCl2·3H2O hydrate as the pretreatment reagent and water-compatible metal salts - ErCl3 as the catalyst, into lactic acid (LA), which is an important chemical building-block widely utilized in the food industry and in the production of chemicals and biodegradable plastic. With 94.0 % conversion of cellulose, an impressive LA yield of 84.6 % was achieved at 170 °C after 4 h under ambient air pressure in water. High yields of LA were also obtained from other carbohydrates, such as fructose (68.3 %), glucose (52.7 %), starch (54.4 %), and inulin (67 %). A series of experiments demonstrated that Er(III) combination with water catalyzed cascading steps of soluble cellulose into LA after ZnCl2·3H2O hydrate disrupted the hydrogen bonds in the cellulose, Zn(II) played an indirect role by promoting LA formation through inhibition of side reactions. A plausible mechanism was proposed for the chemocatalytic conversion of cellulose to LA.


Assuntos
Celulose , Cloretos , Ácido Láctico , Compostos de Zinco , Celulose/química , Cloretos/química , Compostos de Zinco/química , Ácido Láctico/química , Catálise , Hidrólise , Água/química , Sais/química
16.
Eur J Pharm Biopharm ; 203: 114464, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39181416

RESUMO

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C17H19F3N3O3·C4H5O6·2(H2O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL.


Assuntos
Estabilidade de Medicamentos , Fleroxacino , Solubilidade , Tartaratos , Tartaratos/química , Fleroxacino/química , Testes de Sensibilidade Microbiana/métodos , Molhabilidade , Difração de Raios X/métodos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Staphylococcus aureus/efeitos dos fármacos , Sais/química , Química Farmacêutica/métodos
17.
Microbiol Res ; 288: 127869, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39154602

RESUMO

Hypersaline environments are extreme habitats with a limited prokaryotic diversity, mainly restricted to halophilic or halotolerant archaeal and bacterial taxa adapted to highly saline conditions. This study attempts to analyze the taxonomic and functional diversity of the prokaryotes that inhabit a solar saltern located at the Atlantic Coast, in Isla Cristina (Huelva, Southwest Spain), and the influence of salinity on the diversity and metabolic potential of these prokaryotic communities, as well as the interactions and cooperation among the individuals within that community. Brine samples were obtained from different saltern ponds, with a salinity range between 19.5 % and 39 % (w/v). Total prokaryotic DNA was sequenced using the Illumina shotgun metagenomic strategy and the raw sequence data were analyzed using supercomputing services following the MetaWRAP and SqueezeMeta protocols. The most abundant phyla at moderate salinities (19.5-22 % [w/v]) were Methanobacteriota (formerly "Euryarchaeota"), Pseudomonadota and Bacteroidota, followed by Balneolota and Actinomycetota and Uroviricota in smaller proportions, while at high salinities (36-39 % [w/v]) the most abundant phylum was Methanobacteriota, followed by Bacteroidota. The most abundant genera at intermediate salinities were Halorubrum and the bacterial genus Spiribacter, while the haloarchaeal genera Halorubrum, Halonotius, and Haloquadratum were the main representatives at high salinities. A total of 65 MAGs were reconstructed from the metagenomic datasets and different functions and pathways were identified in them, allowing to find key taxa in the prokaryotic community able to synthesize and supply essential compounds, such as biotin, and precursors of other bioactive molecules, like ß-carotene, and bacterioruberin, to other dwellers in this habitat, lacking the required enzymatic machinery to produce them. This work shed light on the ecology of aquatic hypersaline environments, such as the Atlantic Coast salterns, and on the dynamics and factors affecting the microbial populations under such extreme conditions.


Assuntos
Archaea , Bactérias , Metagenômica , Salinidade , Bactérias/genética , Bactérias/classificação , Archaea/genética , Archaea/classificação , Espanha , Água do Mar/microbiologia , Filogenia , Oceano Atlântico , Biodiversidade , Sais , Microbiota/genética , Ecossistema , Metagenoma
18.
Molecules ; 29(16)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39202988

RESUMO

PURPOSE: Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is a well-known penetration enhancer widely used in commercial applications. This study aims to broaden its properties through a novel strategy of converting it into its phenolate salts. The objective is to investigate the synthesis of SNAC phenolate salts, specifically SNAC-choline (SNAC-CH), SNAC-sodium (SNAC-Na), and SNAC-phosphatidylcholine (SNAC-PC), and to explore their potential application in improving the oral absorption of semaglutide. METHODS: The synthesis of SNAC phenolate salts was confirmed through 1H-NMR, FTIR, and an elemental analysis of C, H, N, and O. In vivo testing was conducted to assess the oral delivery of semaglutide using these synthesized SNAC phenolate salts. Pharmacokinetic (PK) values were measured to evaluate the impact on drug absorption. RESULTS: The synthesis of SNAC phenolate salts (SNAC-CH, SNAC-Na, and SNAC-PC) was successfully achieved under appropriate conditions, and their structures were confirmed using analytical techniques such as IR, NMR, and CHN elemental analysis. The paradigm of their use was evaluated through an oral pharmacokinetic (PK) in vivo study using SNAC phenolate salts, which did not impair the original SNAC PK values. This suggests that this strategy holds promise as a potential new effective enhancer for oral absorption. CONCLUSIONS: The utilization of SNAC phenolate salts presents a novel and promising strategy for extending the verity of penetration enhancers' molecules and properties. Synthesizing phenolate salts represents a new chemical strategy that may open new avenues in molecular development. This approach holds future potential to enhance the oral delivery of peptide drugs like semaglutide without compromising therapeutic efficacy. Overall, it offers significant advancements in the field by providing a potential alternative to injectable peptides through oral delivery systems.


Assuntos
Disponibilidade Biológica , Caprilatos , Peptídeos Semelhantes ao Glucagon , Peptídeos Semelhantes ao Glucagon/farmacocinética , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/química , Administração Oral , Animais , Caprilatos/química , Sais/química , Ratos , Masculino
19.
Mol Pharm ; 21(9): 4700-4707, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39108016

RESUMO

This study examines pharmaceutically acceptable inorganic salts of memantine, specifically focusing on hydrogen sulfate, sulfate, and dihydrogen phosphate salts, with the aim of finding alternatives to the commonly used chloride salt in the treatment of Alzheimer's disease. Through comprehensive solid-state characterization, including powder X-ray diffraction, thermal analysis, and solubility testing, we unveil complex polymorphic behaviors, reversible solid-state transitions, and significant differences in solubility and stability among the salts. Notably, the hydrogen sulfate salt emerges as a promising candidate for drug formulations, offering improved solubility, nonhygroscopic nature, and favorable morphological characteristics compared to the existing chloride salt. This work establishes a foundation for further investigation into memantine salts as potential therapeutics with improved efficacy.


Assuntos
Ânions , Composição de Medicamentos , Memantina , Solubilidade , Difração de Raios X , Memantina/química , Ânions/química , Composição de Medicamentos/métodos , Difração de Raios X/métodos , Sais/química , Química Farmacêutica/métodos , Sulfatos/química , Doença de Alzheimer/tratamento farmacológico , Estabilidade de Medicamentos , Varredura Diferencial de Calorimetria/métodos
20.
Astrobiology ; 24(8): 795-812, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39159437

RESUMO

The abundance of potentially habitable hypersaline environments in our solar system compels us to understand the impacts of high-salt matrices and brine dynamics on biosignature detection efforts. We identified and quantified organic compounds in brines from South Bay Salt Works (SBSW), where evapoconcentration of ocean water enables exploration of the impact of NaCl- and MgCl2-dominated brines on the detection of potential biosignature molecules. In SBSW, organic biosignature abundance and distribution are likely influenced by evapoconcentration, osmolyte accumulation, and preservation effects. Bioluminescence assays show that adenosine triphosphate (ATP) concentrations are higher in NaCl-rich, low water activity (aw) samples (<0.85) from SBSW. This is consistent with the accumulation and preservation of ATP at low aw as described in past laboratory studies. The water-soluble small organic molecule inventory was determined by using microchip capillary electrophoresis paired with high-resolution mass spectrometry (µCE-HRMS). We analyzed the relative distribution of proteinogenic amino acids with a recently developed quantitative method using CE-separation and laser-induced fluorescence (LIF) detection of amino acids in hypersaline brines. Salinity trends for dissolved free amino acids were consistent with amino acid residue abundance determined from the proteome of the microbial community predicted from metagenomic data. This highlights a tangible connection up and down the "-omics" ladder across changing geochemical conditions. The detection of water-soluble organic compounds, specifically proteinogenic amino acids at high abundance (>7 mM) in concentrated brines, demonstrates that potential organic biomarkers accumulate at hypersaline sites and suggests the possibility of long-term preservation. The detection of such molecules in high abundance when using diverse analytical tools appropriate for spacecraft suggests that life detection within hypersaline environments, such as evaporates on Mars and the surface or subsurface brines of ocean world Europa, is plausible and argues such environments should be a high priority for future exploration. Key Words: Salts-Analytical chemistry-Amino acids-Biosignatures-Capillary electrophoresis-Preservation. Astrobiology 24, 795-812.


Assuntos
Exobiologia , Meio Ambiente Extraterreno , Sais , Exobiologia/métodos , Meio Ambiente Extraterreno/química , Sais/análise , Sais/química , Trifosfato de Adenosina/análise , Trifosfato de Adenosina/metabolismo , Aminoácidos/análise , Salinidade , Compostos Orgânicos/análise , Voo Espacial , Água do Mar/química , Água do Mar/microbiologia , Água do Mar/análise
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