RESUMO
The Bauhinia ungulata, also known by its common name "pata de vaca", is one of the species used in Brazil for medicinal purposes, and is commonly used for the treatment of diabetes. In this study, the authors studied the interaction between the chemical constituents which are present in the essential oil of Bauhinia ungulata (EOBU), collected in Boa Vista-RR, Legal Amazon, and their effects on the enzyme acetylcholinesterase (AChE) in the essential oil. The analysis that we perform includes proton magnetic resonance ( 1H NMR), enzymatic inhibition, molecular docking, in silico toxicity prediction, enrichment analysis, and target prediction for biological interactions. According to the tests performed on the essential oil, it obtained 100% inhibition of the enzyme AChE. During 1H NMR experiments, it was found that α- Bisabolol, one of the main components, had a significant alteration in its chemical shift. A molecular docking analysis confirmed that this compound binds to the AChE enzyme, which confirms the 1H NMR analysis. The results of this work showed that the major component of EOBU acted as a possible inhibitor of AChE enzyme in vitro and in silico assays. These results show that EOBU could be potentially applied in Alzheimer's disease treatment.
Assuntos
Acetilcolinesterase , Bauhinia , Inibidores da Colinesterase , Simulação de Acoplamento Molecular , Óleos Voláteis , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Bauhinia/química , Brasil , Acetilcolinesterase/metabolismo , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Simulação por Computador , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/químicaRESUMO
Here, we presented a second-order scattering sensor based on the Zn0.97La0.03O compound (LaZnO) for selective and stable detection of glycated albumin (GA, glycemic long-term biomarker). The LaZnO sample was obtained through the co-precipitation method and then characterized using microscopic and spectroscopic techniques. Furthermore, the selectivity, molecular interference, temporal stability, and pH effects of the LaZnO SOS signal in the absence and presence of GA were investigated. The results indicate the stability of the SOS signal over more than 60 days. Assays conducted within the pH range of 5 to 8 indicate that the detection of GA remains unaffected under the given conditions. Selectivity studies show that the SOS signal of LaZnO is reduced only upon contact with GA, while interference studies show that detection is not affected by other chemical species. Additionally, the calibration curve test showed high sensitivity of the material, with a detection limit of 0.55 µg/ml. All the results suggest that LaZnO can deliver efficiency, selectivity, accuracy, and fast response as a GA biosensor, emphasizing LaZnO's usefulness in detecting protein biomarkers.
Assuntos
Albumina Sérica Glicada , Produtos Finais de Glicação Avançada , Albumina Sérica/metabolismo , Biomarcadores , Zinco , GlicemiaRESUMO
Metal encapsulation delivers a straightforward strategy to improve miscellaneous nanoparticle properties and qualifies the resulting nanocomposite for exceptional application, including bioimaging, drug release, and theranostic development. Besides crucial applications, investigations associated with the nanocomposite impact on the biological media are highly relevant from a pharmacological viewpoint. Such studies can be conducted by exploring nanocomposite attributes and all aspects of their interaction with proteins existing in biofluids. Based on these aspects, the present work examines manganese-encapsulated carbonaceous nanocomposite (MnCQD) and their interaction with plasma proteins. On one side, the obtained nanocomposite has almost spherical shapes (≈12 nm in size), an appropriate composition and interesting optical properties for bioimaging applications. On another side, MnCQD quenches the fluorescence of two plasma proteins (BSA and HTF) following a static mechanism, confirming the formation of the MnCQD-BSA and MnCQD-HTF complexes. Although hydrophobic forces guide the stability of both formed complexes, MnCQD binds preferentially to BSA compared to HTF, with affinity constants differing by almost an order of magnitude. Furthermore, HTF and BSA underwent modifications in their secondary structure provoked due to contact with the nanocomposite, which also presented neglectable opsonization levels when exposed to appropriate biological media. These results highlight the MnCQD outstanding potential to be employed in diverse bioapplications.Communicated by Ramaswamy H. Sarma.
Assuntos
Manganês , Nanocompostos , Opsonização , Fluorescência , Proteínas Sanguíneas , Nanocompostos/química , Soroalbumina Bovina/química , Ligação Proteica , Espectrometria de FluorescênciaRESUMO
The ability to bind plasma proteins helps in comprehending relevant aspects related to the pharmacological properties of many drugs. Despite the vital role of the drug mubritinib (MUB) in the prophylaxis of various diseases, its interaction with carrier proteins still needs to be clarified. The present work focuses on the interaction between MUB and Human serum albumin (HSA), investigated by employing multispectroscopic, biochemical, and molecular docking approaches. The results reveal that MUB has quenched HSA intrinsic fluorescence (following a static mechanism) by attaching very close (r = 6.76 Å) and with moderate affinity (Kb ≈ 104 M-1) to the protein site I (mainly by H-bonds, hydrophobic and Van der Waals forces). On one side, the HSA-MUB interaction has been accompanied by a slight disturbance in the HSA chemical environment (around the Trp residue) and protein secondary structure modifications. On another side, MUB competitively inhibits HSA esterase-like activity, which is very similar to other Tyrosine kinase inhibitors, and evidence that protein functional alterations have been triggered by MUB interaction. In summary, all of the presented observations can shed light on diverse pharmacological factors associated with drug administration.
Assuntos
Albumina Sérica Humana , Humanos , Albumina Sérica Humana/química , Simulação de Acoplamento Molecular , Sítios de Ligação , Ligação Proteica , Transporte de Elétrons , Espectrometria de Fluorescência , Termodinâmica , Dicroísmo CircularRESUMO
Egletes viscosa is a plant with therapeutic value due to its antibacterial, antinociceptive and gastroprotective properties. This study aimed to purify, characterize, and evaluate the cytotoxicity of a lectin (EgviL) from the floral capitula of E. viscosa. The lectin was isolated from saline extract through precipitation with ammonium sulfate followed by Sephadex G-75 chromatography. The molecular mass and isoelectric point (pI) of EgviL were determined as well as its temperature and pH stability. Physical-chemical parameters of interaction between EgviL and carbohydrates were investigated by fluorescence quenching and 1H nuclear magnetic resonance (NMR). Cytotoxicity was investigated against human peripheral blood mononuclear cells (PBMCs) and neoplastic cells. EgviL (28.8 kDa, pI 5.4) showed hemagglutinating activity stable towards heating until 60 °C and at the pH range 5.0-7.0. This lectin is able to interact through hydrophobic and electrostatic bonds with galactose and glucose, respectively. EgviL reduced the viability of PBMCs only at the highest concentration tested (100 µg/mL) while was toxic to Jurkat E6-1 cells with IC50 of 24.1 µg/mL,inducing apoptosis. In summary, EgviL is a galactose/glucose-binding protein with acidic character, stable to heating and with cytotoxic effect on leukemic cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Leucócitos Mononucleares/citologia , Lectinas de Plantas/farmacologia , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Precipitação Química , Estabilidade de Medicamentos , Galactose/metabolismo , Glucose/metabolismo , Testes de Hemaglutinação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Ponto Isoelétrico , Células Jurkat , Leucócitos Mononucleares/efeitos dos fármacos , Células MCF-7 , Lectinas de Plantas/químicaRESUMO
Many skin disorders and diseases are related to tyrosinase activity, in particular, due to the vital role played by this enzyme in the melanogenic process. Although numerous natural and synthetic tyrosinase inhibitors have been published, substantial efforts have been made to understand the influence of tyrosinase inhibition on the viability of melanoma cells. Here, we assess the impact of two keto-derivatives: 2-acetyl-furan (F1), furfural-acetone (F2), and two carboxyl-derivatives: 2-furan-acrylic acid (F3), 5-methyl-2-furan-acrylic acid (F4), on the mushroom tyrosinase (mTYR) activity, by applying spectroscopic, kinetic and theoretical techniques. From an exploratory and theoretical point of view, results indicated that albeit all furans bind tightly to and inhibit mTYR very efficient, carboxyl-furan derivatives presented best inhibitory activities than keto- derivatives and performed the inhibition competitively and reversible. Moreover, we examined the influence of carboxyl derivative on the viability of melanoma cells. Results expose differential toxicity of these furan derivatives, which indicates a piece of evidence that furan inhibition activity may be related to its toxicity against B16F10 cells.