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1.
Microb Pathog ; 144: 104127, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32169485

RESUMO

Despite the main strategy to overcome bacterial resistance has focused on the development of more potent antimicrobial agents, the evolutionary pressure caused by such drugs makes this strategy limited. Molecules that interfere with virulence factors appear as a promising alternative though, as they cause reduced selective pressure. As a matter of fact, staphyloxanthin biosynthesis inhibition (STXBI) has been pursued as promising strategy to reduce S. aureus virulence. Herein, we report the inhibitory profile of 27 tetrangomycin derivatives over staphyloxanthin production. The experimental result showed that naphthoquinone dehydro-α-lapachone (25 - EC50 = 57.29 ± 1.15 µM) and 2-Isopropylnaphtho[2,3-b]furan-4,9-dione (26 EC50 = 82.10 ± 1.09 µM) are the most potent compounds and suggest that hydrogen acceptor groups and lipophilic moieties decorating the naphthoquinone ring are crucial for STXBI. In addition, we present an in situ analysis, through RAMAN spectroscopy, that is inexpensive and might be employed to probe the mechanism of action of staphyloxanthin biosynthesis inhibitors. Therefore, our molecular simplification strategies afforded promising lead compounds for the development of drugs that modulate S. aureus staphyloxanthin biosynthesis.


Assuntos
Antibacterianos/farmacologia , Naftoquinonas/farmacologia , Staphylococcus aureus/metabolismo , Xantofilas/metabolismo , Benzo(a)Antracenos/química , Benzo(a)Antracenos/farmacologia , Farmacorresistência Bacteriana Múltipla , Naftalenos/química , Naftalenos/farmacologia , Naftoquinonas/química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/biossíntese
2.
Front Pharmacol ; 12: 669370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079463

RESUMO

Monoamine oxidases (MAO) are a valuable class of mitochondrial enzymes with a critical role in neuromodulation. In this study, we investigated the effect of natural MAO inhibitors on novel environment-induced anxiety by using the zebrafish novel tank test (NTT). Because zebrafish spend more time at the bottom of the tank when they are anxious, anxiolytic compounds increase the time zebrafish spend at the top of the tank and vice versa. Using this paradigm, we found that harmane, norharmane, and 1,2,3,4-tetrahydroisoquinoline (TIQ) induce anxiolytic-like effects in zebrafish, causing them to spend more time at the top of the test tank and less time at the bottom. 2,3,6-trimethyl-1,4-naphtoquinone (TMN) induced an interesting mix of both anxiolytic- and anxiogenic-like effects during the first and second halves of the test, respectively. TIQ was unique in having no observable effect on general movement. Similarly, a reference MAO inhibitor clorgyline-but not pargyline-increased the time spent at the top in a concentration-dependent manner. We also demonstrated that the brain bioavailability of these compounds are high based on the ex vivo bioavailability assay and in silico prediction models, which support the notion that the observed effects on anxiety-like behavior in zebrafish were most likely due to the direct effect of these compounds in the brain. This study is the first investigation to demonstrate the anxiolytic-like effects of MAO inhibitors on novel environment-induced anxiety in zebrafish.

3.
Exp Ther Med ; 20(5): 82, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32968439

RESUMO

The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-RasG12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-RasG12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and ß-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

4.
J Biotechnol ; 265: 109-115, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29191666

RESUMO

Plant carnivory results from the adaptation of plants to their environment. The capture and digestion of preys, followed by their assimilation by the plant is a source of additional nutrients to overcome scarce nutrient in poor soils. Nepenthes are highly studied carnivorous plants and have developed a number of ecological traits which have attracted the attention of plant biologists. Multiple adaptive strategies developed by these plants make them a source of inspiration for many applications ranging from therapeutic treatments to biocontrol solution in agriculture. The outstanding tissue organization of the digestive pitcher can help to create new and original materials usable in everyday life. In this review article, we propose a state of the art of the latest studies carried out on these particular plants and we establish a list of potential tracks for their exploitation.


Assuntos
Caryophyllales , Animais , Biotecnologia , Carnivoridade , Humanos , Controle Biológico de Vetores
5.
FEBS Lett ; 592(13): 2220-2226, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29885280

RESUMO

In this work, we investigated electron transport around the photosynthetic pigment-protein complex of Photosystem I (PS I) mediated by external high-potential electron carrier 2,3-dichloro-1,4-naphtoquinone (Cl2 NQ) and ascorbate. It has been demonstrated that the oxidized species of Cl2 NQ and ascorbate serve as intermediates capable of accepting electrons from the iron-sulfur cluster FX of PS I. Reduced species of Cl2 NQ and ascorbate are oxidized by photooxidized PS I primary donor P700+ and/or by molecular oxygen. We have found the synergistic effect of Cl2 NQ and ascorbate on the rate of P700+ reduction. Accelerated electron flow to P700+, observed in the presence of both Cl2 NQ and ascorbate, is explained by an increase in the reduced species of Cl2 NQ due to electron transfer from ascorbate.


Assuntos
Ácido Ascórbico/farmacologia , Transporte de Elétrons/efeitos dos fármacos , Naftoquinonas/farmacologia , Complexo de Proteína do Fotossistema I/efeitos dos fármacos , Complexo de Proteína do Fotossistema I/metabolismo , Elétrons , Cinética , Luz , Oxirredução/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Synechocystis
6.
Int. j. morphol ; 36(3): 1016-1021, Sept. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-954224

RESUMO

To determine the effects of 70 % ethanolic extract of Eleutherine bulbosa (Mill.) L. bulbs contained naphtoquinone in blood pressure and lipids profile level of ovariectomized rats. Thin layer chromatography was performed to analyze the content of the Eleutherine bulbosa (Mill.) bulbs extracts using Chloroform : Methanol (7:1) as eluent. This study used white female Sprague-Dawley rats which were divided into 6 groups: SHAM and OVX, both given 0.5 % carboxymethyl cellulose; the positive control group that was given tamoxifen (0.36 mg/200 g B.W.); the three various of doses of extract namely dose 1, 2, and 3 that were given 8, 12, and 18 mg/200 g BW respectively on day 29 until 50. All groups were ovariectomized on day 1, except sham group. Measurement of blood pressure were performed on the day before ovariectomy using non-invasive tool CODA®; and on the second, third, and fourth weeks post-ovariectomy. Three weeks after treatment of hypoestrogen rats by the dose 18 mg/200 g B.W, Eleutherine bulbosa extracts could decrease the systolic blood pressure level to 28.06 %, the diastolic to 30.47 %. Lipid profile of Dose 3 also showed recovery of Triglyceride, LDL and also Total Cholesterol. Eleutherine bulbosa extracts could improve blood pressure of ovariectomized rats by controlling lipids profile level.


Para determinar los efectos del 70 % de extracto etanólico de Eleutherine bulbosa (Mill.) L. en bulbos que contenían naftoquinona, se analizó la presión arterial de ratas ovariectomizadas. Se realizó un estudio de cromatografía de capa fina para analizar el contenido de los extractos de bulbos de Eleutherine bulbosa (Mill.) usando cloroformo:metanol (7:1) como diluyente. En este estudio se utilizaron ratas blancas Sprague-Dawley hembras, que se dividieron en 6 grupos: SHAM y OVX, ambos grupos fueron administrados con carboximetilcelulosa al 0,5 %; grupo control positivo, recibió tamoxifeno (0,36 mg / 200 g de B.W.); y tres grupos restantes, que recibieron tres dosis diferentes de extracto, es decir, dosis 1, 2 y 3 a las que se les administró 8, 12 y 18 mg / 200 g de por peso, respectivamente el día 29 hasta el día 50. Todos los grupos fueron sometidos a ovariectomía en el día 1, excepto el grupo simulado. La medición de la presión arterial se realizó el día anterior a la ovariectomía con la herramienta no invasiva CODA®, y, posteriormente, en la segunda, tercera y cuarta semanas de realizada la ovariectomía. Tres semanas después del tratamiento aplicado a las ratas hipoestrógenas, con la dosis de 18 mg / 200 g por peso, los extractos de Eleutherine bulbosa podrían disminuir el nivel de presión arterial sistólica al 28,06 %, y la diastólica al 30,47 %. La dosis 3 del perfil lipídico mostró mejoría en los niveles de Triglicéridos, LDL y Colesterol Total. Los extractos de Eleutherine bulbosa podrían mejorar la presión sanguínea de ratas ovariectomizadas controlando el nivel del perfil lipídico.


Assuntos
Animais , Feminino , Ratos , Pressão Sanguínea/efeitos dos fármacos , Extratos Vegetais/farmacologia , Naftoquinonas/farmacologia , Iridaceae/química , Extratos Vegetais/química , Ovariectomia , Cromatografia em Camada Fina , Naftoquinonas/análise , Ratos Sprague-Dawley , Estrogênios/deficiência , Lipídeos/análise
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