RESUMO
Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Polímeros/química , Fototerapia/métodos , Nanopartículas/uso terapêutico , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Linhagem Celular TumoralRESUMO
Staphylococcus aureus (S. aureus) infection is a major infectious skin disease that is highly resistant to conventional antibiotic treatment and host immune defense, leading to recurrence and exacerbation of bacterial infection. Herein, we developed a photoresponsive carbon monoxide (CO)-releasing nanocomposite by integrating anion-π+ type-I photosensitizer (OMeTBP) and organometallic complex (FeCO) for the treatment of planktonic S. aureus and biofilm-associated infections. After optimizing the molar ratio of FeCO and OMeTBP, the prepared nanoparticles, OMeTBP@FeCONPs, not only ensured sufficient loading of CO donors and efficient CO generation but also showed negligible free ROS leakage under light irradiation, which helped to avoid tissue damage caused by excessive ROS. Both in vitro and in vivo results demonstrated that OMeTBP@FeCONPs could effectively inhibit S. aureus methicillin-resistant S. aureus (MRSA), and bacterial biofilm. Our design has the potential to overcome the resistance of conventional antibiotic treatment and provide a more effective option for bacterial infections.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Dermatopatias Infecciosas , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Monóxido de Carbono/farmacologia , Monóxido de Carbono/uso terapêutico , Espécies Reativas de Oxigênio , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in-situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC-) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of CuII to CuI through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.
RESUMO
The nucleus is considered the ideal target for anti-tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear-targeted material MeTPAE with aggregation-induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti-tumor activity, which offered new opportunities for the effective treatment of malignant tumors.
Assuntos
Neoplasias , Fotoquimioterapia , Pontos de Checagem do Ciclo Celular , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Ferroptosis regulates cell death through reactive oxygen species (ROS)-associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual-targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor-acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual-targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis-related diseases.
Assuntos
Núcleo Celular/metabolismo , Corantes Fluorescentes/química , Gotículas Lipídicas/metabolismo , Ferroptose , Corantes Fluorescentes/síntese química , Humanos , Gotículas Lipídicas/química , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismoRESUMO
Bioactive peptides derived from proteins generally need to be folded into secondary structures to activate downstream signaling pathways. However, synthetic peptides typically form random-coils, thus losing their bioactivities. Here, we show that by introducing a self-assembling peptide motif and using different preparation pathways, a peptide from insulin-like growth factor-I (IGF-1) can be folded into an α-helix and ß-sheet. The ß-sheet one exhibits a low dissociation constant to the IGF-1 receptor (IGF-1R, 11.5 nM), which is only about 3 times higher than that of IGF-1 (4.3 nM). However, the α-helical one and the peptide without self-assembling motif show weak affinities to IGF-1R ( KD = 179.1 and 321.6 nM, respectively). At 10 nM, the ß-sheet one efficiently activates the IGF-1 downstream pathway, significantly enhancing HUVEC proliferation and preventing cell apoptosis. The ß-sheet peptide shows superior performance to IGF-1 in vivo, and it improves ischemic hind-limb salvage by significantly reducing muscle degradation and enhancing limb vascularization. Our study provides a useful strategy to constrain peptides into different conformations, which may lead to the development of supramolecular nanomaterials mimicking biofunctional proteins.
Assuntos
Fator de Crescimento Insulin-Like I/química , Nanofibras/química , Peptídeos/química , Receptor IGF Tipo 1/química , Apoptose/genética , Proliferação de Células/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanoestruturas/química , Conformação Proteica em alfa-Hélice/efeitos dos fármacos , Conformação Proteica em Folha beta/efeitos dos fármacos , Dobramento de Proteína/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Protected by the host cells, the hidden intracellular bacteria are typically difficult to kill by common antibiotics and cannot be visualized without complex cellular pretreatments. Herein, we successfully developed a bacteria-metabolizable dual-functional probe TPEPy-d-Ala, which is based on d-alanine and a photosensitizer with aggregation-induced emission for fluorescence turn-on imaging of intracellular bacteria in living host cells and photodynamic ablation inâ situ. Once metabolically incorporated into bacterial peptidoglycan, the intramolecular motions of TPEPy-d-Ala are inhibited, leading to an enhanced fluorescent signal, which allows the clear visualization of the intracellular bacteria. Moreover, TPEPy-d-Ala can effectively ablate the labeled intracellular bacteria inâ situ owing to covalent ligation to peptidoglycan, yielding a low intracellular minimum inhibitory concentration (MIC) of 20±0.5â µg mL-1 , much more efficient than that of a commonly used antibiotic, vancomycin.
Assuntos
Bactérias/efeitos dos fármacos , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/farmacologia , Espaço Intracelular/microbiologia , Animais , Corantes Fluorescentes/química , Camundongos , Células RAW 264.7 , Coloração e Rotulagem , Estilbenos/química , Estilbenos/metabolismo , Estilbenos/farmacologiaRESUMO
Tumor-associated macrophages (TAMs) that exist in tumor microenvironment promote tumor progression and have been suggested as a promising therapeutic target for cancer therapy in preclinical studies. Development of theranostic systems capable of specific targeting, imaging, and ablation of TAMs will offer clinical benefits. Here we constructed a theranostic probe, namely, TPE-Man, by attaching mannose moieties to a red-emissive and AIE (aggregation-induced emission)-active photosensitizer. TPE-Man can specifically recognize a mannose receptor that is overexpressed on TAMs by the sugar-receptor interaction and enables fluorescent visualization of the mannose-receptor-positive TAMs in high contrast. The histologic study of mouse tumor sections further verifies TPE-Man's excellent targeting specificity being comparable with the commercial mannose-receptor antibody. TAMs can be effectively eradicated upon exposure to white light irradiation via a photodynamic therapy effect. To our knowledge, this is the first small molecular theranostic probe for TAMs that revealed combined advantages of low cost, high targeting specificity, fluorescent light-up imaging, and efficient photodynamic ablation.
Assuntos
Compostos de Benzilideno/farmacologia , Macrófagos/efeitos dos fármacos , Manosídeos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/efeitos da radiação , Compostos de Benzilideno/toxicidade , Manosídeos/síntese química , Manosídeos/efeitos da radiação , Manosídeos/toxicidade , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Ratos Sprague-Dawley , Nanomedicina Teranóstica/métodosRESUMO
The Chrysanthemum morifolium flower is widely used in China and Japan as a food, beverage, and medicine for many diseases. In our work, two new caffeoylquinic acid derivatives (1, 2), a new flavanone glycoside (3), and six reported flavanones (4â»9) were isolated and identified from the flowers of C. morifolium. The chemical structures of all isolates were elucidated by the analysis of comprehensive spectroscopic data as well as by comparison with previously reported data. The isolated constituents 1â»8 were evaluated for their neuroprotective activity, and compounds 3 and 4 displayed neuroprotective effects against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.
Assuntos
Chrysanthemum/química , Flavanonas , Flores/classificação , Glicosídeos , Fármacos Neuroprotetores , Ácido Quínico/análogos & derivados , Flavanonas/química , Flavanonas/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Células Hep G2 , Humanos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Ácido Quínico/química , Ácido Quínico/farmacologiaRESUMO
Metabolic glycoengineering of unnatural glycans with bio-orthogonal chemical groups and a subsequent click reaction with fluorescent probes have been widely used in monitoring various bioprocesses. Herein, we developed a dual-responsive metabolic precursor that could specifically generate unnatural glycans with azide groups on the membrane of targeted cancer cells with high selectivity. Moreover, a water-soluble fluorescent light-up probe with aggregation-induced emission (AIE) was synthesized, which turned its fluorescence on upon a click reaction with azide groups on the cancer cell surface, enabling special cancer cell imaging with low background signal. Furthermore, the probe can generate 1O2 upon light irradiation, fulfilling its dual role as an imaging and therapeutic agent for cancer cells. Therefore, the concepts of the cancer-cell-specific metabolic precursor cRGD-S-Ac3ManNAz and the AIE light-up probe are promising in bio-orthogonal labeling and cancer-specific imaging and therapy.
Assuntos
Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Luz , Linhagem Celular Tumoral , Química Click , Corantes Fluorescentes/síntese química , Células HEK293 , Humanos , Estrutura Molecular , Solubilidade , Água/químicaRESUMO
Progress in photoacoustic (PA) and magnetic resonance imaging (MRI) bimodal contrast agents has been achieved mainly by utilizing the imaging capability of single or multiple components and consequently realizing the desired application for both imaging modalities. However, the mechanism of the mutual influence between components within a single nanoformulation, which is the key to developing high-performance multimodal contrast agents, has yet to be fully understood. Herein, by integrating conjugated polymers (CPs) with iron oxide (IO) nanoparticles using an amphiphilic polymer, a bimodal contrast agent named CP-IO is developed, displaying 45% amplified PA signal intensity as compared to bare CP nanoparticle, while the performance of MRI is not affected. Further experimental and theoretical simulation results reveal that the addition of IO nanoparticles in CP-IO nanocomposites contributes to this PA signal amplification through a synergistic effect of additional heat generation and faster heat dissipation. Besides, the feasibility of CP-IO nanocomposites acting as PA-MRI bimodal contrast agents is validated through in vivo tumor imaging using mice models. From this study, it is demonstrated that a delicately designed structural arrangement of various components in a contrast agent could potentially lead to a superior performance in the imaging capability.
Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Técnicas Fotoacústicas/métodos , Animais , Linhagem Celular Tumoral , Análise de Elementos Finitos , Camundongos , Nanocompostos/química , Nanopartículas/química , Polímeros/químicaRESUMO
Liposomes have been used as popular drug delivery systems for cancer therapy. However, it is difficult to track traditional liposome delivery systems in an efficient and stable fashion to assess their delivery efficacy and biodistribution after administration. Meanwhile, conventional fluorescent liposomes containing optical tracers face the challenge of aggregation-caused quenching. Herein, we report a strategy for the integration of an aggregation-induced emission fluorogen with a liposome to yield an AIEgen-lipid conjugate, termed "AIEsome". The AIEsome exhibits bright red fluorescence along with great photostability and biocompatibility, and can be used for inâ vitro cancer cell labeling and inâ vivo tumor targeting. Meanwhile, benefiting from the excellent photosensitizing ability of the AIEgen and its good oxygen exposure in aqueous media, the AIEsome also performs well in efficient photodynamic therapy (PDT) for both inâ vitro cancer cell ablation and inâ vivo antitumor therapy after white light illumination.
Assuntos
Corantes Fluorescentes/administração & dosagem , Lipídeos/química , Lipossomos/química , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Corantes Fluorescentes/farmacocinética , Corantes Fluorescentes/uso terapêutico , Camundongos , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/uso terapêutico , Distribuição TecidualRESUMO
Bio-orthogonal tumor labeling is more effective in delivering imaging agents or drugs to a tumor site than active targeting strategy owing to covalent ligation. However, to date, tumor-specific imaging through bio-orthogonal labeling largely relies on body clearance to differentiate target from the intrinsic probe signal owing to the lack of light-up probes for inâ vivo bio-orthogonal labeling. Now the first light-up probe based on a fluorogen with aggregation-induced emission for inâ vivo bio-orthogonal fluorescence turn-on tumor labeling is presented. The probe has low background fluorescence in aqueous media, showing negligible non-specific interaction with normal tissues. Once it reacts with azide groups introduced to tumor cells through metabolic engineering, the probe fluorescence is lightened up very quickly, enabling rapid tumor-specific imaging. The photosensitizing ability was also used to realize effective image-guided photodynamic tumor therapy.
Assuntos
Corantes Fluorescentes/química , Luz , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Camundongos , Estrutura MolecularRESUMO
A glycoside hydrolase from Penicillium oxalicum BL 3005 was purified to apparent homogeneity. Its molecular mass was estimated to be 90 kDa by SDS-PAGE. The enzyme was identified to be a new member of family-3 by peptide sequence. High transglycosylation activity was found in the hydrolytic reaction of cellobiose. In the reaction, salidroside (4-hydroxyphenethyl O-ß-d-glucopyranoside) was formed by adding tyrosol as the glycosyl acceptor. The optimum reaction pH and temperature were pH 6.5 and 55 °C, respectively. The maximum yield of salidroside was almost 20 g/L. These results indicated that the ß-glucosidase of P. oxalicum can be considered as a very promising catalyst for the synthesis of salidroside.
Assuntos
Biocatálise , Glucosídeos/biossíntese , Glicosídeo Hidrolases/metabolismo , Penicillium/enzimologia , Álcool Feniletílico/análogos & derivados , Eletroforese em Gel de Poliacrilamida , Glucosídeos/química , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/isolamento & purificação , Glicosilação , Peso Molecular , Fenóis/química , Álcool Feniletílico/química , Álcool Feniletílico/metabolismoRESUMO
We report in this study on optimized ratiometric fluorescent probes by peptide self-assembly. The resulting self-assembled nanoprobes show extraordinary stability in aqueous solutions and extremely low background fluorescence in buffer solutions. Our optimized probes with much bigger ratiometric fluorescence ratios also show an enhanced cellular uptake, lower background noise, and much brighter fluorescence signal in the cell experiment. Our study provides a versatile and very useful strategy to design and produce fluorescent probes with better performance.
Assuntos
Corantes Fluorescentes/química , Peptídeos/química , Peptídeos/síntese química , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Hidrazinas/análise , Sulfeto de Hidrogênio/análise , Microscopia de Fluorescência , Estrutura MolecularRESUMO
BACKGROUND/AIMS: Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery. METHODS: SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and α-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined. RESULTS AND CONCLUSION: Accelerated wound healing and enhanced local capillary regeneration could be observed 14 days after skin ablation from both SKPs and collagen sponge co-transplanted and collagen sponge only groups. Subsequent analyses further revealed superior pro-angiogenic effects from the SKP and collagen sponge co-delivered group, which are mainly attributable to in vivo transdifferentation and paracrine signalling of the SKPs.
Assuntos
Colágeno/farmacologia , Regeneração/fisiologia , Dermatopatias/terapia , Pele/metabolismo , Transplante de Células-Tronco , Cicatrização/efeitos dos fármacos , Animais , Capilares/fisiologia , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Comunicação Parácrina/efeitos dos fármacos , Pele/patologia , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
OBJECTIVES: To investigate the conversion of lutein, a carotenoid, to aroma compounds by Pantoea dispersa Y08, a lutein-degrading bacterium isolated from marigold flower residue. Bioconversion conditions, including substrate concentration, applied co-solvent and reaction time, were optimized. RESULTS: A maximum biodegradation yield of 80 % for lutein at 10 g/l was achieved. The intermediate, 3-hydroxy-ß-ionone, and final ß-ionone products were revealed by GC-MS. A bioconversion pathway of lutein is proposed to involve cleavage at the 9-10 double bond position, followed by de-hydroxylation at the 3-hydroxy position. CONCLUSIONS: This is the first report of the ability of a bacterium, P. dispersa, to sequentially convert lutein to 3-hydroxy-ß-ionone and then ß-ionone.
Assuntos
Luteína/metabolismo , Norisoprenoides/metabolismo , Pantoea/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Biotransformação , Cromatografia Gasosa-Espectrometria de Massas , Redes e Vias MetabólicasRESUMO
We demonstrate that the incorporation of one or two amino acids of phenylalanine (F) or 4-fluoro phenylalanine ((f)F) will greatly lower the background fluorescence intensities of conventional quenched probes with quenchers. This enhanced quenching effect was due to the synergetic effect of the aggregation caused quenching and the presence of a quencher. Such strategy will not greatly affect the enzyme recognition properties to the probes. We also demonstrated that our self-assembled nanoprobe with the enhanced quenching effect showed a better performance in cells for the detection of cell apoptosis than the unassembled probes. Our study demonstrates that using molecular self-assembly can optimize and improve the performance of molecular probes and it provides a simple but very useful strategy to boost the signal-to-noise ratios of fluorescence probes.
Assuntos
Sondas Moleculares/química , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/toxicidade , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Microscopia Confocal , Sondas Moleculares/metabolismo , Sondas Moleculares/toxicidade , Peptídeos/síntese química , Peptídeos/química , Peptídeos/metabolismo , Rodaminas/química , Rodaminas/metabolismo , Rodaminas/toxicidade , Razão Sinal-RuídoRESUMO
The major nutrients, pH and temperature were evaluated for the exopolysaccharide (EPS) production by Daedalea dickinsii in submerged culture to derive an optimal medium composition and conditions as follows: 50 g/L maltose, 5 g/L soy peptone, 5 mM CaCl(2), at pH 6.0 and 28 °C. A purified EPS fraction was attained from gel filtration chromatography and its major molecular characteristics were determined. FT-IR spectral analysis revealed the prominent characteristic groups of polyhydric alcohols. GC analysis and NMR spectrum showed its major molecular composition of glucose and galactose. Furthermore, thermogravimetric analysis indicated its degradation temperature (T(d)) of 189 °C. The antioxidant activity of the EPS fraction showed a correlation with the molecular properties. It might be attributed to the functional groups in the EPS fraction, which can donate electrons to reduce the radicals to a more stable form or react with the free radicals to terminate the radical chain reaction.
Assuntos
Antioxidantes/química , Polissacarídeos/biossíntese , Basidiomycota/metabolismo , Biomassa , Reatores Biológicos , Carbono/química , Cromatografia Gasosa , Cromatografia em Gel , Fermentação , Radicais Livres , Galactose/química , Glucose/química , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Micélio/metabolismo , Nitrogênio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , TermogravimetriaRESUMO
Two new megastigmane glycosides, (6 R,7E,9R)-3-oxo-α-ionyl-9-O-α-L-rhamnopyranosyl-(1''â4')-ß-D-glucopyranoside (1) and (6 R,7E,9R)-3-oxo-α-ionyl-9-O-ß-D-glucopyranosyl-(1''â6')-ß-D-glucopyranoside (2), together with six known analogues (3-8) were isolated from the leaves of Nicotiana tabacum. The structures of all metabolites were determined by comprehensive analysis of NMR and MS spectroscopic data as well as by comparison with those of previously reported. The in vitro anti-inflammatory activity of all isolates was evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model, and the compounds 1, 3, 7, and 8 exhibited inhibition of LPS-induced NO production in RAW264.7 macrophage cells with IC50 values of 42.3-61.7 µM (positive control, dexamethasone, IC50 = 21.3 ± 1.2 µM).