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1.
Polymers (Basel) ; 14(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36235941

RESUMO

The use of natural polysaccharides as biomaterials is gaining importance in tissue engineering due to their inherent biocompatibility. In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. This marine bacterium produces 17.3 g/L of EPS at 96 h of fermentation. The EPS was purified using ion exchange and gel permeation chromatographic methods. The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. AFM analysis revealed spike-like lumps with a surface roughness of 84.85 nm. The zeta potential value of −10 mV indicates the anionic nature of the EPS. Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). The polymer has an average molecular weight of 555 kDa. Further, NMR analysis revealed the monomer composition, the existence of two α- and six ß-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-ß-D-Glcp-(1 → 5)]-ß-D-Frup-(2 → 2)[ß-D-Xylp-(1 → 4)]-ß-D-Xylp-(1 → 6)-ß-D-Fruf-(2 → 4)-ß-D-Ribp-(1 →. The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. Our research unveils the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials.

2.
Carbohydr Res ; 505: 108326, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34015720

RESUMO

The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of antivirals has been evolved as a suitable strategy in the current treatment and preventive measures. The concept of drug repurposing represents new experimental approaches for effective therapeutic benefits. Besides, SARS-CoV-2 exhibits several complications such as lung damage, blood clot formation, respiratory illness and organ failures in most of the patients. Based on the accumulation of data, sulfated marine polysaccharides have exerted successful inhibition of virus entry, attachment and replication with known or unknown possible mechanisms against deadly animal and human viruses so far. Since the virus entry into the host cells is the key process, the prevention of such entry mechanism makes any antiviral strategy effective. Enveloped viruses are more sensitive to polyanions than non-enveloped viruses. Besides, the viral infection caused by RNA virus types embarks severe oxidative stress in the human body that leads to malfunction of tissues and organs. In this context, polysaccharides play a very significant role in providing shielding effect against the virus due to their polyanionic rich features and a molecular weight that hinders their reactive surface glycoproteins. Significantly the functional groups especially sulfate, sulfate pattern and addition, uronic acids, monosaccharides, glycosidic linkage and high molecular weight have greater influence in the antiviral activity. Moreover, they are very good antioxidants that can reduce the free radical generation and provokes intracellular antioxidant enzymes. Additionally, polysaccharides enable a host-virus immune response, activate phagocytosis and stimulate interferon systems. Therefore, polysaccharides can be used as candidate drugs, adjuvants in vaccines or combination with other antivirals, antioxidants and immune-activating nutritional supplements and antiviral materials in healthcare products to prevent SARS-CoV-2 infection.


Assuntos
Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Fatores Imunológicos/uso terapêutico , Polissacarídeos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Phaeophyceae/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/virologia , Insuficiência Respiratória/complicações , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/virologia , Rodófitas/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Ésteres do Ácido Sulfúrico/química , Ligação Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
3.
Carbohydr Res ; 487: 107881, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31805426

RESUMO

Oxidative damage caused by free radicals is an inevitable and pervasive phenomenon that leads to cell damage and the emergence of diseases including ageing, cancer, diabetes, cardiovascular disease and neurodegenerative disorders. In this context, antioxidants play a significant role in encountering free radicals by delaying or reducing the oxidative damage of cells. Evidence suggests that synthetic antioxidants are double-edged swords wherefore the requirement for natural antioxidants is increasing globally. Exploring non-toxic, biodegradable and compatible natural molecules like exopolysaccharides can favour the current antioxidant limitations. Microbial exopolysaccharides represent a structurally diverse class of carbohydrate molecules secreted at the cell wall. Recently, bioprospecting exopolysaccharides for their astounding physiochemical properties and the reliable structure-activity relationship have motivated more research towards the investigation of their antioxidant properties. Here we propose that structural features of exopolysaccharides such as monosaccharide residues, branching, molecular weight, glycosidic linkage, functional groups, protein, selenium, and chemical modifications are likely to influence their antioxidant activity. To support this hypothesis we review the interdependence of structural features of exopolysaccharides to the observed antioxidant activity. In light of its importance, this review focuses on the understanding of the elimination of free radicals by microbial exopolysaccharides derived from marine and nonmarine sources during the last six years.


Assuntos
Antioxidantes/farmacologia , Polissacarídeos Bacterianos/farmacologia , Animais , Antioxidantes/síntese química , Antioxidantes/química , Configuração de Carboidratos , Radicais Livres/antagonistas & inibidores , Humanos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos Bacterianos/síntese química , Polissacarídeos Bacterianos/química
4.
Mol Inform ; 37(12): e1800048, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30051592

RESUMO

Developing a new antibacterial drug by using (Z/E)-4-(4-substituted-benzylidene)-2-isoquinoline-1,3(2H,4H)-diones (5a-h) via DNA gyrase inhibition mechanism is the main aim of this study. DNA gyrase inhibition assay was executed to confirm the DNA gyrase inhibition potentials of 5a-h. DNA gyrase inhibitory potentials were further validated through molecular docking. Docking study was also intended to get more insight into the binding mode of 5a-h into the active site of DNA gyrase A. Agar well diffusion method antimicrobial activity on Gram-ve bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), and Gram+ve bacteria (Staphylococcus aureus (MTCC 96) and Streptococcus pyogenes (MTCC 442) was evaluated. Excellent DNA gyrase inhibition was exhibited by the compound 5c, IC50 0.55±0.12 µM; 5d, IC50 0.65±0.075 µg/mL; 5e, IC50 0.45±0.035 µM; 5f, IC50 0.58±0.025 µM; 5h, IC50 0.25±0.015 µM while Clorobiocin (standard) showed IC50 0.5±0.05 µM. Apart from all the in vitro studies, a plausible mechanism of DNA gyrase inhibition was also proposed through the in silico validations that are including molecular docking, predicted SAR, functional group availability, pharmacokinetic, and ADMET properties. These predictions are well supported to confirm the druggability possibility of the most potent compounds among (Z/E)-4-(4-substituted-benzylidene)-2-isoquinoline-1,3(2H,4H) -diones (5a-h).


Assuntos
Antibacterianos/química , Proteínas de Bactérias/química , DNA Girase/química , Descoberta de Drogas/métodos , Simulação de Acoplamento Molecular/métodos , Inibidores da Topoisomerase II/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Compostos de Benzilideno/química , Sítios de Ligação , DNA Girase/metabolismo , Isoquinolinas/química , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Inibidores da Topoisomerase II/farmacologia
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