RESUMEN
Solution blowing process was used to prepare cellulose nonwovens, by using N-methyl morpholine-N-oxide (NMMO) as solvent, and salicylic acid (SA) microcapsules as antibacterial additives. The structure and properties of cellulose nonwovens modified with different SA microcapsules contents were compared and evaluated. The results showed that more uniform and denser web structure was formed with the increase of SA microcapsules content, the average fiber diameter of cellulose nonwoven increased from 1.99 µm to 2.65 µm. The air flow resistance and filtration efficiency of cellulose nonwovens increased with addition of SA microcapsules, whereas the mechanical properties, and wearing comfort including air permeability, moisture vapor transfer rate, and softness of cellulose nonwovens decreased slightly, under the same basis weight. SA microcapsules modified cellulose nonwovens exhibited good sustained-release behavior and antimicrobial activity against Escherichia coli. The higher SA microcapsules content in cellulose nonwovens, the faster release rate and the higher antimicrobial activity. The cellulose solution-blown nonwovens modified with SA microcapsules are expected to find applications in medical and healthcare fields due to its antibacterial activity and biodegradability.
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Antibacterianos , Cápsulas , Celulosa , Escherichia coli , Ácido Salicílico , Solventes , Celulosa/química , Ácido Salicílico/química , Ácido Salicílico/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Solventes/química , Liberación de Fármacos , Óxidos N-Cíclicos/química , Soluciones , Pruebas de Sensibilidad MicrobianaRESUMEN
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 crustaceansâArtemia 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.
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Acné Vulgar , Antibacterianos , Simulación del Acoplamiento Molecular , Niacinamida , Acné Vulgar/tratamiento farmacológico , Niacinamida/química , Niacinamida/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Solubilidad , Salicilatos/química , Salicilatos/farmacología , Pruebas de Sensibilidad Microbiana , Sales (Química)/química , Propionibacteriaceae/efectos de los fármacos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Aniones/química , Ácido Salicílico/química , Ácido Salicílico/farmacologíaRESUMEN
Salicylic acid is a commonly used anti-spoilage agent to prevent browning and quality degradation during potato processing, yet its precise mechanism remains unclear. This study elucidates the role of StuPPO2, a functional protein in Favorita potato shreds, in relation to the anti-browning and starch degradation effects of 52 SA analogues. By employing molecular docking and Gaussian computing, SA localizes within the hydrophobic cavity of StuPPO2, facilitated by hydroxyl and carboxyl groups. The inhibitory effect depends on the distribution pattern of the maximal electrostatic surface potential, requiring hydroxyl ion potentials of >56 kcal/mol and carboxyl ion potentials of >42 kcal/mol, respectively. Multiomics analysis, corroborated by validation tests, indicates that SA synthetically suppresses activities linked to defense response, root regeneration, starch degradation, glycoalkaloids metabolism, and potato shred discoloration, thereby preserving quality. Furthermore, SA enhances antimicrobial and insect-repellent aromas, thereby countering biotic threats in potato shreds. These collective mechanisms underscore SA's anti-spoilage properties, offering theoretical foundations and potential new anti-browning agents for agricultural preservatives.
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Ácido Salicílico , Solanum tuberosum , Solanum tuberosum/química , Solanum tuberosum/metabolismo , Ácido Salicílico/química , Ácido Salicílico/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Simulación del Acoplamiento Molecular , Tubérculos de la Planta/química , Conservantes de Alimentos/farmacología , Conservantes de Alimentos/química , Manipulación de Alimentos , Conservación de Alimentos/métodosRESUMEN
Solid-liquid extraction was investigated to obtain selected major plant nutrients (P, K, Ca, Mg) from biofuel ash using weak organic acids like salicylic acid, citric acid, and oxalic acid as sacrificial leaching agents. In this study, three organic acids were compared to determine the most effective leaching agent for maximizing the P, K, Ca, and Mg extraction from biofuel ash. The findings indicated that 0.1 M citric acid was the most efficient for plant nutrient recovery, with 81.9% of P recovered after 30 min, 82.4% of Ca, 76.8% of Mg, and 47.3% of K. after 120 min. The highest amount of K, with 59.3% was recovered after 180 min of extraction with 0.1 M oxalic acid. However, recovery of P-80.7% was lower, and much lower recovery of Ca-2.3%, and Mg-68.6% after 180 min of extraction with 0.1 M oxalic acid. The leachates were not contaminated with heavy metals, just 0.47 mg/L of Zn, 7.67 mg/L of Al, and 1.99 mg/L of Fe were detected after 180 min of extraction with 0.1 M oxalic acid. The formation of calcium oxalates after extraction with 0.1 M oxalic acid was seen by SEM-EDS. The findings indicated that to achieve the highest recovery of all beneficial nutrients (P, K, Ca, Mg) different extraction times and different extraction agents are required.
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Biocombustibles , Ácido Oxálico , Ácido Oxálico/química , Biocombustibles/análisis , Ácido Cítrico/química , Nutrientes/análisis , Metales Pesados/análisis , Metales Pesados/química , Fósforo/análisis , Fósforo/química , Magnesio/química , Magnesio/análisis , Ácido Salicílico/química , Calcio/química , Calcio/análisis , Potasio/análisis , Potasio/químicaRESUMEN
Background: Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research. Methods: In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner. Results: We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of -64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP's ability to improve tumor characterization and diagnostic precision. Conclusion: The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.
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Fluorocarburos , Hematoporfirinas , Imagen por Resonancia Magnética , Nanopartículas , Poliésteres , Ácido Salicílico , Fluorocarburos/química , Imagen por Resonancia Magnética/métodos , Animales , Poliésteres/química , Nanopartículas/química , Humanos , Ácido Salicílico/química , Ácido Salicílico/farmacocinética , Ácido Salicílico/administración & dosificación , Hematoporfirinas/química , Hematoporfirinas/farmacocinética , Hematoporfirinas/farmacología , Ratones , Ultrasonografía/métodos , Medios de Contraste/química , Medios de Contraste/farmacocinética , Línea Celular Tumoral , Imagen Multimodal/métodos , PentanosRESUMEN
This study investigates how wheat gluten (WG) films in the presence of salicylic acid are influenced by thermal pretreatment. Unlike previous methods conducted at low moisture content, our procedure involves pretreating WG at different temperatures (65 °C, 75 °C, and 85 °C), in a solution with salicylic acid. This pretreatment aims to enhance protein unfolding, thus providing more opportunities for protein-protein interactions during the subsequent solvent casting into films. A significant increase in ß-sheet structures was observed in FTIR spectra of samples pretreated at 75 °C and 85 °C, showing a prominent peak in the range of 1630-1640 cm-1. The pretreatment at 85 °C was found to be effective in improving the water resistivity of the films by up to 247 %. Moreover, it led to a significant enhancement of 151 % in tensile strength and a 45 % increase in the elastic modulus. The reduced solubility observed in films derived from pretreated WG suggests the development of an intricate protein network arising from protein-protein interactions during the pretreatment and film formation. Thermal pretreatment at 85 °C significantly enhances the structural and mechanical properties of WG films, including improved water resistivity, tensile strength, and intricate protein network formation.
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Glútenes , Calor , Ácido Salicílico , Resistencia a la Tracción , Ácido Salicílico/química , Glútenes/química , Solubilidad , Agua/química , Triticum/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Considerable effort has been invested in developing salicylic acid (SA) biosensors for various application purposes. Here, by engineering the sensing modules and host cell chassis, we have gradually optimized the NahR-Psal/Pr-based SA biosensor, increasing the sensitivity and maximum output by 17.2-fold and 9.4-fold, respectively, and improving the detection limit by 800-fold, from 80 µM to 0.1 µM. A portable SA sensing device was constructed by embedding a gelatin-based hydrogel containing an optimized biosensor into the perforations of tape adhered to glass slide, which allowed good determination of SA in the range of 0.1 µM-10 µM. Then, we developed a customized smartphone App to measure the fluorescence intensity of each perforation and automatically calculate the corresponding SA concentration so that we could detect SA concentrations in real cosmetic samples. We anticipate that this smartphone-based imaging biosensor, with its compact size, higher sensitivity, cost-effectiveness, and easy data transfer, will be useful for long-term monitoring of SA.
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Técnicas Biosensibles , Límite de Detección , Ácido Salicílico , Teléfono Inteligente , Técnicas Biosensibles/instrumentación , Ácido Salicílico/análisis , Ácido Salicílico/química , Diseño de Equipo , Humanos , Hidrogeles/química , Cosméticos/química , Cosméticos/análisisRESUMEN
Crystallization is a widely used purification technique in the manufacture of active pharmaceutical ingredients (APIs) and precursor molecules. However, when impurities and desired compounds have similar molecular structures, separation by crystallization may become challenging. In such cases, some impurities may form crystalline solid solutions with the desired product during recrystallization. Understanding the molecular structure of these recrystallized solid solutions is crucial to devise methods for effective purification. Unfortunately, there are limited analytical techniques that provide insights into the molecular structure or spatial distribution of impurities that are incorporated within recrystallized products. In this study, we investigated model solid solutions formed by recrystallizing salicylic acid (SA) in the presence of anthranilic acid (AA). These two molecules are known to form crystalline solid solutions due to their similar molecular structures. To overcome challenges associated with the long 1H longitudinal relaxation times (T1(1H)) of SA and AA, we employed dynamic nuclear polarization (DNP) and 15N isotope enrichment to enable solid-state NMR experiments. Results of solid-state NMR experiments and DFT calculations revealed that SA and AA are homogeneously alloyed as a solid solution. Heteronuclear correlation (HETCOR) experiments and plane-wave DFT structural models provide further evidence of the molecular-level interactions between SA and AA. This research provides valuable insights into the molecular structure of recrystallized solid solutions, contributing to the development of effective purification strategies and an understanding of the physicochemical properties of solid solutions.
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Isótopos de Carbono , Cristalización , Espectroscopía de Resonancia Magnética , Isótopos de Nitrógeno , Ácido Salicílico , ortoaminobenzoatos , Espectroscopía de Resonancia Magnética/métodos , Ácido Salicílico/química , Cristalización/métodos , Isótopos de Nitrógeno/química , ortoaminobenzoatos/química , Isótopos de Carbono/química , Soluciones/química , Estructura MolecularRESUMEN
A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.
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Sistemas de Liberación de Medicamentos , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Salicilatos , Ácido Salicílico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Salicilatos/administración & dosificación , Salicilatos/química , Salicilatos/farmacocinética , Ácido Láctico/química , Sistemas de Liberación de Medicamentos/métodos , Ácido Salicílico/administración & dosificación , Ácido Salicílico/química , Ácido Salicílico/farmacocinética , Ácido Poliglicólico/química , Liberación de Fármacos , Administración Tópica , Química Farmacéutica/métodos , Administración Cutánea , Concentración de Iones de Hidrógeno , Solubilidad , Preparaciones de Acción Retardada , Piel/metabolismoRESUMEN
Aspirin is a commonly used nonsteroidal anti-inflammatory drug, associated with many adverse effects. The adverse effects of aspirin such as tinnitus, Reye's syndrome and gastrointestinal bleeding are caused due to conversion of aspirin into its active metabolite salicylic acid after oral intake. Glutathione is a naturally occurring antioxidant produced by the liver and nerve cells in the central nervous system. It helps to metabolize toxins, break down free radicles, and support immune function. This study aims to investigate and explore the possibility of inhibiting aspirin to salicylic acid conversion in presence of glutathione at a molecular level using spectroscopic techniques such as UV-Visible absorption, time-Resolved and time-dependent fluorescence and theoretical DFT/ TD-DFT calculations. The results of steady state fluorescence spectroscopy and time-dependent fluorescence indicated that the aspirin to salicylic acid conversion is considerably inhibited in presence of glutathione. Further, the results presented here might have significant clinical implications for individuals with variations in glutathione level.
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Aspirina , Teoría Funcional de la Densidad , Glutatión , Ácido Salicílico , Espectrometría de Fluorescencia , Aspirina/farmacología , Aspirina/química , Aspirina/metabolismo , Glutatión/metabolismo , Glutatión/química , Ácido Salicílico/metabolismo , Ácido Salicílico/química , Ácido Salicílico/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Fluorescencia , Estructura MolecularRESUMEN
The Expert Panel for Cosmetic Ingredient Safety (Panel) reassessed the safety of Capryloyl Salicylic Acid in cosmetic products; this ingredient is reported to function as a skin conditioning agent. The Panel reviewed relevant data relating to the safety of this ingredient in cosmetic formulations, and concluded that the available data are insufficient to make a determination that Capryloyl Salicylic Acid is safe under the intended conditions of use in cosmetic formulations.
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Seguridad de Productos para el Consumidor , Cosméticos , Salicilatos , Animales , Humanos , Cosméticos/toxicidad , Cosméticos/química , Medición de Riesgo , Salicilatos/toxicidad , Salicilatos/farmacocinética , Ácido Salicílico/toxicidad , Ácido Salicílico/farmacocinética , Ácido Salicílico/química , Pruebas de ToxicidadRESUMEN
Case studies are needed to demonstrate the use of human-relevant New Approach Methodologies in cosmetics ingredient safety assessments. For read-across assessments, it is crucial to compare the target chemical with the most appropriate analog; therefore, reliable analog selection should consider physicochemical properties, bioavailability, metabolism, as well as the bioactivity of potential analogs. To complement in vitro bioactivity assays, we evaluated the suitability of three potential analogs for the UV filters, homosalate and octisalate, according to their in vitro ADME properties. We describe how technical aspects of conducting assays for these highly lipophilic chemicals were addressed and interpreted. There were several properties that were common to all five chemicals: they all had similar stability in gastrointestinal fluids (in which no hydrolysis to salicylic occurred); were not substrates of the P-glycoprotein efflux transporter; were highly protein bound; and were hydrolyzed to salicylic acid (which was also a major metabolite). The main properties differentiating the chemicals were their permeability in Caco-2 cells, plasma stability, clearance in hepatic models, and the extent of hydrolysis to salicylic acid. Cyclohexyl salicylate, octisalate, and homosalate were identified suitable analogs for each other, whereas butyloctyl salicylate exhibited ADME properties that were markedly different, indicating it is unsuitable. Isoamyl salicylate can be a suitable analog with interpretation for octisalate. In conclusion, in vitro ADME properties of five chemicals were measured and used to pair target and potential analogs. This study demonstrates the importance of robust ADME data for the selection of analogs in a read-across safety assessment.
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Salicilatos , Humanos , Salicilatos/toxicidad , Salicilatos/farmacocinética , Salicilatos/química , Células CACO-2 , Medición de Riesgo , Protectores Solares/toxicidad , Protectores Solares/farmacocinética , Protectores Solares/química , Disponibilidad Biológica , Ácido Salicílico/farmacocinética , Ácido Salicílico/química , Ácido Salicílico/toxicidad , Cosméticos/toxicidad , Cosméticos/químicaRESUMEN
Encapsulation of active pharmaceutical ingredients (APIs) in confined spaces has been extensively explored as it dramatically alters the molecular dynamics and physical properties of the API. Herein, we explored the effect of encapsulation on the molecular dynamics and physical stability of a guest drug, salicylic acid (SA), confined in the intermolecular spaces of γ-cyclodextrin (γ-CD) and poly(ethylene glycol) (PEG)-based polypseudorotaxane (PPRX) structure. The sublimation tendency of SA encapsulated in three polymorphic forms of the γ-CD/PEG-based PPRX complex, monoclinic columnar (MC), hexagonal columnar (HC), and tetragonal columnar (TC), was investigated. The SA sublimation rate was decreased by 3.0-6.6-fold and varied in the order of MC form > HC form > TC form complex. The 13C and 1H magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectra and 13C spin-lattice relaxation time (T1) indicated that the encapsulated SA molecules existed as the monomeric form, and its molecular mobility increased in the order of MC form > HC form > TC form complex. In the complexes, a rapid chemical exchange between two dynamic states of SA (free and bound) was suggested, with varying adsorption/desorption rates accounting for its distinct molecular mobility. This adsorption/desorption process was influenced by proton exchange at the interaction site and interaction strength of SA in the complexes, as evidenced by 1H MAS spectra and temperature dependency of the 13C carbonyl chemical shift. A positive correlation between the molecular mobility of SA and its sublimation rate was established. Moreover, the molecular mobility of γ-CD and PEG in the complexes coincided with that of SA, which can be explained by fast guest-driven dynamics. This is the first report on the stability improvement of an API through complexation in polymorphic supramolecular host structures. The relationship between the molecular dynamics and physical properties of encapsulated API will aid in the rational design of drug delivery systems.
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Ciclodextrinas , Simulación de Dinámica Molecular , Poloxámero , Rotaxanos , Preparaciones Farmacéuticas , Ciclodextrinas/química , Espectroscopía de Resonancia Magnética , Ácido Salicílico/químicaRESUMEN
Salicylic acid is a raw material for preparing aspirin and holds an important position in medical history. Studying the crystallization of these two drugs is of great significance in improving their dissolution rate, bioavailability, and physical stability. Although various techniques have been used for structural characterization, there is still a lack of information on the collective vibrational behavior of aspirin and salicylic acid eutectic compounds. Firstly, two starting materials (salicylic acid and aspirin) were ground in a 1:1 M ratio to prepare eutectic compounds. The eutectic composition was studied using vibrational spectroscopy techniques, such as X-ray powder diffusion (XRPD), terahertz time-domain spectroscopy (THz-TDS), and Raman spectroscopy. Additionally, the structure of the aspirin and salicylic acid eutectic was simulated and optimized using density functional theory. It was found that the eutectic type II was the most consistent with the experiment, and the corresponding vibration modes of each peak were provided. These results offer a unique method for characterizing the structural composition of eutectic crystals, which can be utilized to enhance the physical and chemical properties, as well as the pharmacological activity, of specific drugs at the molecular level.
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Aspirina , Espectroscopía de Terahertz , Aspirina/química , Ácido Salicílico/química , Vibración , Espectrometría RamanRESUMEN
Nonexpressor of pathogenesis-related genes 1 (NPR1) was discovered in Arabidopsis as an activator of salicylic acid (SA)-mediated immune responses nearly 30 years ago. How NPR1 confers resistance against a variety of pathogens and stresses has been extensively studied; however, only in recent years have the underlying molecular mechanisms been uncovered, particularly NPR1's role in SA-mediated transcriptional reprogramming, stress protein homeostasis, and cell survival. Structural analyses ultimately defined NPR1 and its paralogs as SA receptors. The SA-bound NPR1 dimer induces transcription by bridging two TGA transcription factor dimers, forming an enhanceosome. Moreover, NPR1 orchestrates its multiple functions through the formation of distinct nuclear and cytoplasmic biomolecular condensates. Furthermore, NPR1 plays a central role in plant health by regulating the crosstalk between SA and other defense and growth hormones. In this review, we focus on these recent advances and discuss how NPR1 can be utilized to engineer resistance against biotic and abiotic stresses.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácido Salicílico/química , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacología , Factores de Transcripción/metabolismo , Estrés Fisiológico , Regulación de la Expresión Génica de las PlantasRESUMEN
Salicylic acid (SA) is one of the chemical molecules, involved in plant growth and immunity, thereby contributing to the control of pests and pathogens, and even applied in fruit and vegetable preservation. However, only a few tools have ever been designed or executed to understand the physiological processes induced by SA or its function in plant immunity and residue detection in food. Hence, three Rh6G-based fluorogenic chemosensors were synthesized to detect phytohormone SA based on the "OFF-ON" mechanism. The probes showed high selectivity, ultrafast response time (<60 s), and nanomolar detection limit for SA. Moreover, the probe possessed outstanding profiling that can be successfully used for SA imaging of callus and plants. Furthermore, the fluorescence pattern indicated that SA could occur in the distal transport in plants. These remarkable results contribute to improving our understanding of the multiple physiological and pathological processes involved in SA for plant disease diagnosis and for the development of immune activators. In addition, SA detection in some agricultural products used probes to extend the practical application because its use is prohibited in some countries and is harmful to SA-sensitized persons. Interestingly, the as-obtained test paper displayed that SA could be imaged by ultraviolet (UV) and was directly visible to the naked eye. Given the above outcomes, these probes could be used to monitor SA in vitro and in vivo, including, but not limited to, plant biology, food residue detection, and sewage detection.
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Reguladores del Crecimiento de las Plantas , Ácido Salicílico , Ácido Salicílico/química , Ácido Salicílico/farmacología , Reguladores del Crecimiento de las Plantas/químicaRESUMEN
3D printing of pharmaceuticals offers a unique opportunity for long-term, sustained drug release profiles for an array of treatment options. Unfortunately, this approach is often limited by physical compounding or processing limitations. Modification of the active drug into a prodrug compound allows for seamless incorporation with advanced manufacturing methods that open the door to production of complex tissue scaffold drug depots. Here we demonstrate this concept using salicylic acids with varied prodrug structures for control of physical and chemical properties. The role of different salicylic acid derivatives (salicylic acid, bromosalicylic allyl ester, iodosalicylic allyl ester) and linker species (allyl salicylate, allyl 2-(allyloxy)benzoate, allyl 2-(((allyloxy)carbonyl)oxy)benzoate) were investigated using thiol-ene cross-linking in digital light processing (DLP) 3D printing to produce porous prodrug tissue scaffolds containing more than 50% salicylic acid by mass. Salicylic acid photopolymer resins were all found to be highly reactive (solidification within 5 s of irradiation at λ = 405 nm), while the cross-linked solids display tunable thermomechanical behaviors with low glass transition temperatures (Tgs) and elastomeric behaviors, with the carbonate species displaying an elastic modulus matching that of adipose tissue (approximately 65 kPa). Drug release profiles were found to be zero order, sustained release based upon hydrolytic degradation of multilayered scaffolds incorporating fluorescent modeling compounds, with release rates tuned through selection of the linker species. Cytocompatibility in 2D and 3D was further demonstrated for all species compared to polycarbonate controls, as well as salicylic acid-containing composites (physical incorporation), over a 2-week period using murine fibroblasts. The use of drugs as the matrix material for solid prodrug tissue scaffolds opens the door to novel therapeutic strategies, longer sustained release profiles, and even reduced complications for advanced medicine.
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Profármacos , Andamios del Tejido , Ratones , Animales , Andamios del Tejido/química , Ácido Salicílico/química , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Ésteres , Impresión TridimensionalRESUMEN
Salicylic acid (SA) is a key hormone that regulates plant growth and immunity, and understanding the physiologic processes induced by SA enables the development of highly pathogen-resistant crops. Here, we report the synthesis of three new SA-sensors (R1-R3) from hydroxyphenol derivatives of a rhodamine-acylhydrazone scaffold and their characterization by NMR and HRMS. Spectroscopic analyses revealed that structural variations in R1-R3 resulted in sensors with different sensitivities for SA. Sensor R2 (with the 3-hydroxyphenyl modification) outperformed R1 (2-hydroxyphenyl) and R3 (4-hydroxyphenyl). The SA-detection limit of R2 is 0.9 µM with an ultra-fast response time (<60 s). In addition, their plant imaging indicated that designed sensor R2 is useful for the further study of SA biology and the discovery and development of new inducers of plant immunity.
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Células Vegetales , Ácido Salicílico , Rodaminas/química , Ácido Salicílico/análisis , Ácido Salicílico/química , Células Vegetales/química , Colorantes , PlantasRESUMEN
A series of previously synthesized conjugates of tacrine and salicylamide was extended by varying the structure of the salicylamide fragment and using salicylic aldehyde to synthesize salicylimine derivatives. The hybrids exhibited broad-spectrum biological activity. All new conjugates were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. The structure of the salicylamide moiety exerted little effect on anticholinesterase activity, but AChE inhibition increased with spacer elongation. The most active conjugates were salicylimine derivatives: IC50 values of the lead compound 10c were 0.0826 µM (AChE) and 0.0156 µM (BChE), with weak inhibition of the off-target carboxylesterase. The hybrids were mixed-type reversible inhibitors of both cholinesterases and displayed dual binding to the catalytic and peripheral anionic sites of AChE in molecular docking, which, along with experimental results on propidium iodide displacement, suggested their potential to block AChE-induced ß-amyloid aggregation. All conjugates inhibited Aß42 self-aggregation in the thioflavin test, and inhibition increased with spacer elongation. Salicylimine 10c and salicylamide 5c with (CH2)8 spacers were the lead compounds for inhibiting Aß42 self-aggregation, which was corroborated by molecular docking to Aß42. ABTSâ¢+-scavenging activity was highest for salicylamides 5a-c, intermediate for salicylimines 10a-c, low for F-containing salicylamides 7, and non-existent for methoxybenzoylamides 6 and difluoromethoxybenzoylamides 8. In the FRAP antioxidant (AO) assay, the test compounds displayed little or no activity. Quantum chemical analysis and molecular dynamics (MD) simulations with QM/MM potentials explained the AO structure-activity relationships. All conjugates were effective chelators of Cu2+, Fe2+, and Zn2+, with molar compound/metal (Cu2+) ratios of 2:1 (5b) and ~1:1 (10b). Conjugates exerted comparable or lower cytotoxicity than tacrine on mouse hepatocytes and had favorable predicted intestinal absorption and blood-brain barrier permeability. The overall results indicate that the synthesized conjugates are promising new multifunctional agents for the potential treatment of AD.
Asunto(s)
Enfermedad de Alzheimer , Tacrina , Animales , Ratones , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Antioxidantes/farmacología , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Simulación del Acoplamiento Molecular , Salicilamidas , Relación Estructura-Actividad , Tacrina/farmacología , Tacrina/química , Ácido Salicílico/químicaRESUMEN
Ligand inducible proteins that enable precise and reversible control of nuclear translocation of passenger proteins have broad applications ranging from genetic studies in mammals to therapeutics that target diseases such as cancer and diabetes. One of the drawbacks of the current translocation systems is that the ligands used to control nuclear localization are either toxic or prone to crosstalk with endogenous protein cascades within live animals. We sought to take advantage of salicylic acid (SA), a small molecule that has been extensively used in humans. In plants, SA functions as a hormone that can mediate immunity and is sensed by the nonexpressor of pathogenesis-related (NPR) proteins. Although it is well recognized that nuclear translocation of NPR1 is essential to promoting immunity in plants, the exact subdomain of Arabidopsis thaliana NPR1 (AtNPR1) essential for SA-mediated nuclear translocation is controversial. Here, we utilized the fluorescent protein mCherry as the reporter to investigate the ability of SA to induce nuclear translocation of the full-length NPR1 protein or its C-terminal transactivation (TAD) domain using HEK293 cells as a heterologous system. HEK293 cells lack accessory plant proteins including NPR3/NPR4 and are thus ideally suited for studying the impact of SA-induced changes in NPR1. Our results obtained using a stable expression system show that the TAD of AtNPR1 is sufficient to enable the reversible SA-mediated nuclear translocation of mCherry. Our studies advance a basic understanding of nuclear translocation mediated by the TAD of AtNPR1 and uncover a biotechnological tool for SA-mediated nuclear localization.