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1.
Acta Trop ; 188: 1-8, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30145258

RESUMO

Dengue fever is a severe, widespread disease with more than 2 million diagnosed infections per year. The Dengue virus protease represents a cardinal target for prudent drug design. Among the four serotypes Dengue 2 is known for the occurrence of its frequent epidemics. The new compound inhibited the Dengue-2 in the low-micromolar range in cells. At the moment, protease inhibitors are not actively tried against dengue virus as therapeutic option. We have identified thiosemicarbazones derived phenyl-acetyl ketones as candidate for a novel class of protease inhibitors. Here, we report the selective and non-competitive inhibition of the Dengue virus serotype 2 in vitro and in silico. Molecular docking suggests binding at a specific active site. In addition to the docking assays, few techniques were developed to interpret these molecules's antiviral profile in vitro.


Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Serina Endopeptidases , Animais , Domínio Catalítico , Chlorocebus aethiops , Descoberta de Drogas , Simulação de Acoplamento Molecular , Células Vero
2.
Eur J Pharmacol ; 814: 45-55, 2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-28826870

RESUMO

Exploring the importance of nanofibrous scaffold with traditionally important medicine as a wound dressing material prevents infection and aids in faster healing of wounds. In the present study, the Collagen (COL) from the marine fish skin was extracted and employed for coating the Poly(3-hydroxybutyric acid) (P)-Gelatin (G) nanofibrous scaffold with a bioactive Coccinia grandis extract (CPE) fabricated through electrospinning. Further, the fabricated collagen coated nanofibrous scaffold (PG-CPE-COL) applied to the experimental wound of rats and the wound healing was analyzed with by physiochemical and biological techniques. The increased level of hydroxyproline, hexosamine and uronic acid was observed in PG-CPE-COL treated than the other groups. The CPE and collagen in the nanofibrous scaffold accelerates the wound healing and thereby reduced the inflammation caused by the cyclooxygenase-2 (COX-2) and inducible nitric oxide synthases (iNOS) in wound healing. The nanofibrous scaffold has influenced the expression of various growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and transforming growth factor (TGF-ß). In addition, the PG-CPE-COL nanofibrous scaffold increases the deposition of collagen synthesis and accelerates reepithelialization. Thus, the results suggest that the collagen coated nanofibrous scaffold with bioactive traditional medicine enhanced the faster healing of wound.


Assuntos
Materiais Biocompatíveis/farmacologia , Colágeno/química , Citocinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Nanofibras/química , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Ciclo-Oxigenase 2/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hidroxibutiratos/química , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Poliésteres/química , Ratos , Ratos Wistar , Reepitelização/efeitos dos fármacos
3.
J Med Virol ; 89(3): 546-552, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27490721

RESUMO

The endemicity and seasonal outbreaks of Dengue disease in most tropical and subtropical countries underscores an urgent need to develop effective prevention and control measures. Development of a Dengue vaccine, which is complicated by the Antibody Dependent Enhancement effect (ADE), a viral inhibitor, seems prudent as it would inhibit the spread of the virus. In vitro methods such as MTT assay and plaque formation unit reduction assays were employed for screening the viral inhibitory property of α-amino acid based Thiosemicarbazides. The results elicits that at concentrations not exceeding the maximum non cytotoxic concentration (MNCC), these compounds completely prevented Dengue virus infection in vero cells as indicated by the absence of cytopathic effects in a dose-dependent manner. The high potency of Bz-Trp-TSC against all four types of Dengue virus infection elevates Thiosemicarbazide as a lead antiviral agent for Dengue disease. Screening small molecules for antiviral activity against the most rapidly spreading mosquito-borne viral disease is being explored by several research groups. Our findings would help to augment the efforts to identify the lead compounds for antiviral therapy to combat the Dengue disease. J. Med. Virol. 89:546-552, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Tiossemicarbazonas/farmacologia , Animais , Sobrevivência Celular , Chlorocebus aethiops , Efeito Citopatogênico Viral , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade Microbiana , Células Vero , Ensaio de Placa Viral
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