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1.
Bioorg Med Chem Lett ; 29(12): 1459-1462, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31000155

RESUMO

Chagas disease represents one of several neglected diseases with a reduced number of chemotherapeutical drugs including the highly toxic compounds benznidazole and nifurtimox. In this sense, natural products represent an import scaffold for the discovery of new biologically active compounds, in which chalcones are promising representatives due to their antitrypanosomal potential. In this work, a series of 36 chalcone derivatives were synthesized and tested against trypomastigotes of Trypanosoma cruzi. In addition, a detailed investigation on their molecular features was performed. The obtained results suggest that certain molecular features are fundamental for an efficient antitrypanosomal potential of chalcones, such as allylic groups, α,ß-unsaturated carbonyl system, and aromatic hydroxyl groups. These results were obtained based on the interpretation of machine-learning and multivariate statistical methods, which revealed the essential characteristics of chalcone prototypes against trypomastigotes of T. cruzi.


Assuntos
Chalconas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Animais , Chalconas/farmacologia , Análise Multivariada , Relação Estrutura-Atividade
2.
BMC Plant Biol ; 16(1): 156, 2016 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-27405371

RESUMO

BACKGROUND: The developmental and cell death domain (DCD)-containing asparagine-rich proteins (NRPs) were first identified in soybean (Glycine max) as transducers of a cell death signal derived from prolonged endoplasmic reticulum (ER) stress, osmotic stress, drought or developmentally-programmed leaf senescence via the GmNAC81/GmNAC30/GmVPE signaling module. In spite of the relevance of the DCD/NRP-mediated signaling as a versatile adaptive response to multiple stresses, mechanistic knowledge of the pathway is lacking and the extent to which this pathway may operate in the plant kingdom has not been investigated. RESULTS: Here, we demonstrated that the DCD/NRP-mediated signaling also propagates a stress-induced cell death signal in other plant species with features of a programmed cell death (PCD) response. In silico analysis revealed that several plant genomes harbor conserved sequences of the pathway components, which share functional analogy with their soybean counterparts. We showed that GmNRPs, GmNAC81and VPE orthologs from Arabidopsis, designated as AtNRP-1, AtNRP-2, ANAC036 and gVPE, respectively, induced cell death when transiently expressed in N. benthamiana leaves. In addition, loss of AtNRP1 and AtNRP2 function attenuated ER stress-induced cell death in Arabidopsis, which was in marked contrast with the enhanced cell death phenotype displayed by overexpressing lines as compared to Col-0. Furthermore, atnrp-1 knockout mutants displayed enhanced sensitivity to PEG-induced osmotic stress, a phenotype that could be complemented with ectopic expression of either GmNRP-A or GmNRP-B. In addition, AtNRPs, ANAC036 and gVPE were induced by osmotic and ER stress to an extent that was modulated by the ER-resident molecular chaperone binding protein (BiP) similarly as in soybean. Finally, as putative downstream components of the NRP-mediated cell death signaling, the stress induction of AtNRP2, ANAC036 and gVPE was dependent on the AtNRP1 function. BiP overexpression also conferred tolerance to water stress in Arabidopsis, most likely due to modulation of the drought-induced NRP-mediated cell death response. CONCLUSION: Our results indicated that the NRP-mediated cell death signaling operates in the plant kingdom with conserved regulatory mechanisms and hence may be target for engineering stress tolerance and adaptation in crops.


Assuntos
Estresse do Retículo Endoplasmático , Retículo Endoplasmático/metabolismo , Glycine max/metabolismo , Proteínas de Plantas/genética , Transdução de Sinais , Arabidopsis/química , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Evolução Biológica , Retículo Endoplasmático/química , Retículo Endoplasmático/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas/química , Plantas/classificação , Plantas/genética , Plantas/metabolismo , Glycine max/química , Glycine max/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-26737850

RESUMO

An electrocardiograph was designed and implemented, being capable of obtaining electrical signals from the heart, and sending this data via Bluetooth to a tablet, in which the signals are graphically shown. The user interface is developed as an Android application. Because of the technological progress and the increasing use of full portable systems, such as tablets and cell phones, it is important to understand the functioning and development of an application, which provides a basis for conducting studies using this technology as an interface. The project development includes concepts of electronics and its application to achieve a portable and functional final project, besides using a specific programmable integrated circuit for electrocardiogram, electroencephalogram and electromyogram, the ADS1294. Using a simulator of cardiac signals, 36 different waveforms were recorded, including normal sinus rhythm, arrhythmias and artifacts. Simulations include variations of heart rate from 30 to 190 beats per minute (BPM), with variations in peak amplitude of 1 mV to 2 mV. Tests were performed with a subject at rest and in motion, observing the signals obtained and the damage to their interpretation due to the introduction of muscle movement artifacts in motion situations.


Assuntos
Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Microcomputadores , Processamento de Sinais Assistido por Computador/instrumentação , Arritmias Cardíacas/fisiopatologia , Humanos
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