794 research outputs found
Farnesoid X Receptor as a potential protein target for mushroom LMW compounds: virtual screening using molecular docking
Farnesoid X receptor (FXR) is a nuclear receptor protein involved in controlling several metabolic pathways, with bile acids as his natural ligands. FXR functions as a sensor for bile acids, thus promoting their clearance by controlling expression of genes involved in bile acids transport and metabolism. FXR has been recently regarded as an important target for drug discovery and the research for small molecules, that modulates his interaction with binding co-regulator proteins, is ongoing. Very recently, several reports have shown natural compounds and extracts with activity as, either agonists or antagonists of FXR, notably steroids (1) and polyphenols (2). Mushrooms have been widely recognised as presenting in their chemical constitution polyphenols and steroids in significant amounts, either in quantity and diversity. For this reason we set out to investigate FXR as a potential target for LMW compounds present in mushrooms. To meet this goal we virtually screened a database of 40 compounds, present in mushrooms, against a carefully prepared 3D crystal structure of FXR (PDB code: 1OIV). The molecular docking software used for this virtual screening project was AutoDock Vina (VINA) and the database of LMW compounds were revised and prepared by us. VINA presents the results as predΔG (predicted binding energy), with compounds with the lowest predΔG expected to be the ones with more potent FXR modulating activity. Among the tested compounds, steroids presented the lowest predΔG, with several displaying values below -10 kcal/mol including: Ergosta-4,6,8(14),22-tetraen-3-one (-10,5 kcal/mol), Ganoderic acid A (-10,4 kcal/mol), Ganoderic acid A (-10,3 kcal/mol) and Ergosterol (-10,2 kcal/mol). These results are not unexpected, as FXR natural ligands are in fact bile acids, that belong to the steroid class of compounds. Also, the predΔG values of the top ranked steroids compared well with the predΔG value of a benzamide derivative compound (10,6 kcal/mol), a known inhibitor of FXR that is co-crystallized in the 1OIV crystal structure. In conclusion, this initial study points to FXR as a potential target for mushroom compounds and extracts, especially steroid derivatives or extracts. Although further studies are needed to confirm this hypothesis, this work demonstrates the usefulness of using an in silico approach as a complement for experimental work.info:eu-repo/semantics/publishedVersio
Stress oxidativo, antioxidantes e fitoquímicos
A manutenção do equilíbrio entre a produção de
radicais livres e as defesas antioxidantes (enzimas e
moléculas não enzimáticas) é uma condição essencial
para o funcionamento normal do organismo. Quando
este equilíbrio tende para a produção de radicais livres
dizemos que o organismo está em stress oxidativo, e
nestas situações os radicais livres em excesso podem
oxidar e danificar lípidos celulares, proteínas e DNA,
inibindo a sua função normal e conduzindo a várias
doenças. Em organismos aeróbios, os radicais livres são
constantemente produzidos durante o funcionamento
normal da célula, na maior parte sob a forma de
espécies reactivas de oxigénio (ROS) e de nitrogénio
(RNS). A exposição dos organismos a radicais livres,
conduziu ao desenvolvimento de mecanismos de
defesa endógenos para os eliminar. Estas defesas são
a resposta da evolução à inevitabilidade da existência
de ROS em condições aeróbias. Alguns produtos
naturais com actividade antioxidante, podem auxiliar
o sistema protector endógeno. Nesta perspectiva, os
antioxidantes presentes na dieta assumem grande
importância como possíveis agentes protectores,
reduzindo os danos oxidativos. São aqui descritos
alguns desses agentes antioxidantes, os fitoquímicos,
compostos bioactivos provenientes de diferentes partes
de plantas (sementes, cereais, vegetais, frutos, folhas,
raízes, especiarias, ervas) envolvidos na redução do
risco de doença, como o cancro. Foram já identificados
mais de 5000 fitoquímicos, no entanto, grande parte
destes compostos é ainda desconhecida, sendo a sua
identificação essencial para a compreensão da sua
contribuição na saúde, ao serem incluídos na dieta. Maintenance of equilibrium between free radical
production and antioxidant defences (enzymatic and
non enzymatic) is an essential condition for normal
organism functioning. When this equilibrium has a
tendency to the production of free radical we say that
the organism is in oxidative stress. In this situation,
excess free radicals may damage cellular lipids,
proteins and DNA, inhibiting his normal function
and leading to various diseases. In aerobic organisms,
the free radicals are constantly being produced
during the normal cellular functioning, mainly in
the form of Reactive Oxygen Species (ROS) and
Reactive Nitrogen Species (RNS). Exposition of the
organism to free radicals has led to the development of
endogenous defence mechanisms to eliminate them.
These defences were the response of evolution to the
inevitability of ROS production in aerobic conditions.
Natural products with antioxidant activity may help
the endogenous defence system. In this perspective
the antioxidant present on the diet assume a major
importance as possible protector agents reducing
oxidative damage. Phytochemicals with antioxidant
activity, obtained from different plant parts (seeds,
cereals, vegetables, fruits, leaves, roots, spices,
herbs), and involved in disease risk reduction are
review. More than 5000 phytochemicals were already
discovered, but most of these compounds remain yet
to be discovered. Their identification and the study of
their contribution to health is essential
Antioxidants in wild mushrooms
Maintenance of equilibrium between free radical production and antioxidant defences (enzymatic and non enzymatic)
is an essential condition for normal organism functioning. When this equilibrium has a tendency for the production
of free radicals we say that the organism is in oxidative stress. In this situation, excess free radicals may damage cellular
lipids, proteins and DNA, affecting normal function and leading to various diseases. In aerobic organisms, the free
radicals are constantly produced during the normal cellular metabolism, mainly in the form of Reactive Oxygen Species
(ROS) and Reactive Nitrogen Species (RNS). Exposition of the organism to free radicals has led to the development of
endogenous defence mechanisms to eliminate them. These defences were the response of evolution to the inevitability of
ROS production in aerobic conditions. Natural products with antioxidant activity may help the endogenous defence system.
In this perspective the antioxidants present in the diet assume a major importance as possible protector agents reducing
oxidative damage. Particularly, the antioxidant properties of wild mushrooms have been extensively studied by our research
group and by others, and many antioxidant compounds extracted from these sources have been identified, such as
phenolic compounds, tocopherols, ascorbic acid, and carotenoids. We will review the compounds identified so far in
mushrooms, as well as the mechanism of action involved in their antioxidant properties. Wild mushrooms might be used
directly in diet and promote health, taking advantage of the additive and synergistic effects of all the bioactive compounds
present
Virtual ligand screening studies between mushroom compounds and proteins involved in breast cancer
Mushrooms are a vast and yet largely untapped source of powerful new pharmaceutical
products. In particular, and most importantly for modern medicine, they represent an
unlimited source of compounds with antitumor and immunostimulating properties [1].
Particularly, the intake of some wild mushrooms has shown to reduce the risk of breast
cancer in Chinese women [2]. A large number of LMW (low molecular weight)
compounds have been "identified in wild mushrooms including phenolic acids,
flavonoids, tocopherols, carotenoids, sugars and fatty acids [3]. In this study we used
AutoDock 4 [4] to perform virtual ligand screening in order to evaluate which LMW
compounds may be involved in the inhibition of the activity of proteins related to
human breast cancer: aromatase (EC: 1.14.14.1), estrone sulfatase (EC: 3.1.6.2) and 17-
hydroxysteroid dehydrogenase type 1 activity (17~-HSD-1; EC:. 1.1.1.62) [5]. A
representative dataset of 43 LMW compounds was selected and molecular docking was
performed against the three protein targets. 4-0-caffeoylquinic, naringin and lycopene stand out as the top ranked potential inhibitors for aromatase, estrone sulfatase and 1 7~HSD1,
respectively. The information provided shows several interesting starting points
for further development of inhibitors of the studied proteins, as also for the development of nutraceuticals or functional foods
QCAR models to predict wild mushrooms radical scavenging activity, reducing power and lipid peroxidation inhibition
Wild mushrooms have become attractive as a source of physiologically beneficial compounds including antioxidants such as phenolic compounds and tocopherols. The concentrations of antioxidant compounds (phenolics and α-tocopherol) and EC50 values of antioxidant activity (concentration required to achieve 50% of radical scavenging activity and lipid peroxidation inhibition, or 0.5 of absorbance in reducing power) were analyzed by partial least square (PLS) regression analysis. Three QCAR (Quantitative Composition-Activity Relationship) models were constructed and their robustness and predictability were verified by internal and external cross-validation methods. Antioxidant activity correlated well with phenolics and -tocopherol contents, the major antioxidants in wild mushrooms. The models proved to be useful tools in the prediction of mushrooms radical scavenging activity, reducing power and lipid peroxidation inhibition
Using molecular docking to investigate the anti-breast cancer activity of low molecular weight compounds present on wild mushrooms.
Mushrooms represent an unlimited source of compounds with antitumor and immunostimulating properties and mushroom intake as been shown to reduce the risk of breast cancer. A large number of LMW (low molecular weight) compounds present in mushrooms have been identified including: phenolic acids, flavonoids, tocopherols, carotenoids, sugars and fatty acids. In order to evaluate which wild mushroom LMW compounds may be involved in anti-breast cancer activity we selected a representative dataset of 43 LMW compounds and performed molecular docking against 3 known protein targets involved in breast cancer (Aromatase, Estrone Sulfatase and 17β-HSD-1) using AutoDock4 as docking software. The estimated inhibition constants for all LMW compounds were determined and the potential structure-activity relationships for the compounds with the best estimated inhibition constants are discussed for each compound family. 4-O-caffeoylquinic, naringin and lycopene stand out as the top ranked potential inhibitors for Aromatase, Estrone Sulfatase and 17β-HSD1, respectively, and the 3-D docked conformation for these compounds are discussed in detail. This information provides several interesting starting points for further development of Aromatase, Estrone Sulfatase and 17β-HSD1 inhibitors
On the azimuthal asymmetries in DIS
Using the recent experimental data on the left right asymmetry in
fragmentation of transversely polarized quarks and the theoretical calculation
of the proton transversity distribution in the effective chiral quark soliton
model we explain the azimuthal asymmetries in semi-inclusive hadron production
on longitudinal (HERMES) and transversely (SMC) polarized targets with no free
parameters. On this basis we state that the proton transversity distribution
could be successfully measured in future DIS experiments with longitudinally
polarized target.Comment: 8 pages, latex, 5 eps figures, uses epsfig and wrapfi
Valorização de cogumelos silvestres como alimentos funcionais: estudos de química computacional
As interacções intermoleculares desempenham um papel essencial nos diversos processos biológicos, sendo fundamental a compreensão destas interacções nos Sectores das Indústrias Farmacêuticas e de Alimentos Funcionais. Os cogumelos representam uma fonte ilimitada de compostos com propriedades antitumorais e imunoestimulantes, e o seu consumo foi já relacionado com a redução do risco de cancro da mama. No presente trabalho, foram desenvolvidos dois estudos in silico com o intuito de compreender algumas das interacções moleculares presentes em cogumelos e responsáveis pela sua bioactividade.
A técnica dos Mínimos Quadrados Parciais foi utilizada para avaliar a relação entre o potencial antioxidante (efeitos bloqueadores de radicais livres e poder redutor) e a composição química de vinte e três amostras de dezassete espécies de cogumelos silvestres Portugueses. Estudaram-se vários parâmetros analíticos tais como cinzas, hidratos de carbono, proteínas, gorduras, ácidos gordos monoinsaturados, ácidos gordos polinsaturados, ácidos gordos saturados, fenóis, flavonóides, ácido ascórbico e β-caroteno, e os seus resultados foram analisados pela técnica anteriormente mencionada de forma a estabelecer correlações entre todos os parâmetros. A actividade antioxidante mostrou estar correlacionada com o teor em fenóis e flavonóides. Foi construído um modelo QCAR (Relações Quantitativas Composição – Actividade), cuja robustez e previsibilidade foram verificadas por métodos de validação cruzada internos e externos. Finalmente, este modelo provou ser uma ferramenta útil na previsão do poder redutor de cogumelos
QSAR model for predicting radical scavenging activity of di(hetero)arylamines derivatives of benzo[b]thiophenes
A QSAR study was developed in order to model the antioxidant activity, specifically the radical scavenger
activity (RSA), of 26 di(hetero)arylamines’ derivatives of benzo[b]thiophenes. The QSAR model was
constructed, using the partial least squares projection of latent structures (PLS) method, and its
robustness and predictability were verified by internal and external cross-validation methods. A total of 4
molecular descriptors, belonging to RDF (Radial Distribution Function) descriptors (RDF020e and
RDF045e) and 2D-autocorrelation descriptors (GATS8p and MATS5e) were selected to build the QSAR
model. RDF descriptors seem to relate the presence of electronegative atoms at the inner atmosphere of
the compounds to increase RSA. 2D-Autocorrelation descriptors associate the presence of polarizable and
electronegative pairs of atoms, at specific topological distance, with the RSA of the compounds. Finally
this QSAR model proved to be a useful tool in the prediction of radical scavenger activity of congeneric
compounds and will be used to guide the synthesis of new diarylamines in our laboratory
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