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1.
Pharmaceuticals (Basel) ; 17(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38794162

RESUMO

P2X7 is an ATP-activated purinergic receptor implicated in pro-inflammatory responses. It is associated with the development of several diseases, including inflammatory and neurodegenerative conditions. Although several P2X7 receptor antagonists have recently been reported in the literature, none of them is approved for clinical use. However, the structure of the known antagonists can serve as a scaffold for discovering effective compounds in clinical therapy. This study aimed to propose an improved virtual screening methodology for the identification of novel potential P2X7 receptor antagonists from natural products through the combination of shape-based and docking approaches. First, a shape-based screening was performed based on the structure of JNJ-47965567, a P2X7 antagonist, using two natural product compound databases, MEGx (~5.8 × 103 compounds) and NATx (~32 × 103 compounds). Then, the compounds selected by the proposed shape-based model, with Shape-Tanimoto score values ranging between 0.624 and 0.799, were filtered for drug-like properties. Finally, the compounds that met the drug-like filter criteria were docked into the P2X7 allosteric binding site, using the docking programs GOLD and DockThor. The docking poses with the best score values were submitted to careful visual inspection of the P2X7 allosteric binding site. Based on our established visual inspection criteria, four compounds from the MEGx database and four from the NATx database were finally selected as potential P2X7 receptor antagonists. The selected compounds are structurally different from known P2X7 antagonists, have drug-like properties, and are predicted to interact with key P2X7 allosteric binding pocket residues, including F88, F92, F95, F103, M105, F108, Y295, Y298, and I310. Therefore, the combination of shape-based screening and docking approaches proposed in our study has proven useful in selecting potential novel P2X7 antagonist candidates from natural-product-derived compounds databases. This approach could also be useful for selecting potential inhibitors/antagonists of other receptors and/or biological targets.

2.
Anal Methods ; 15(45): 6259-6265, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37955245

RESUMO

This study presents the development of a simple, fast, and inexpensive approach for the direct analysis of new psychoactive substances (NPS) in seized tablets and blotter paper, with improved sample preservation and increased analytical frequency. Paper triangles were gently rubbed against the surface of the samples containing synthetic drugs and then subjected to analysis by paper spray ionization mass spectrometry (PS-MS). Seized samples containing lysergic acid diethylamide (LSD) and several other substances from the classes of amphetamines, N-benzyl-substituted phenethylamines, synthetic cathinones, and synthetic cannabinoids, were analysed. Three types of paper were tested (filter paper, blotter paper, and synthetic paper) and several combinations of spray solvents were studied for the optimization. All samples were weighed and photographed before and after sequences of analysis in order to attest to the sample preservation. The results revealed that the approach is excellent for sample preservation, with less than 5% of mass loss even after 27 consecutive analyses. Moreover, no significant signal decreases were observed in mass spectrometry (MS) even after the experiments. It was possible to unequivocally identify illicit substances from seized samples (pills and blotter paper). By overcoming the solubilization and wet extraction process used for sample preparation, the waste was restricted to a volume of only 10 µL of solvent for the PS-MS analysis. The main advantage of our approach over existing methods is the sample preparation, which is simple and quick since the samples are just rubbed against the PS paper. This brings enormous benefits in terms of analytical frequency, economy of time and low consumption of solvents. Another important point is that the sample can remain intact for further analysis, which is crucial in forensic analysis.


Assuntos
Dietilamida do Ácido Lisérgico , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Dietilamida do Ácido Lisérgico/análise , Dietilamida do Ácido Lisérgico/química , Comprimidos , Solventes
3.
Forensic Sci Int ; 288: 227-235, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29777946

RESUMO

Several new psychoactive substances (NPS) have reached the illegal drug market in recent years, and ecstasy-like tablets are one of the forms affected by this change. Cathinones and tryptamines have increasingly been found in ecstasy-like seized samples as well as other amphetamine type stimulants. A presumptive method for identifying different drugs in seized ecstasy tablets (n=92) using ATR-FTIR (attenuated total reflectance - Fourier transform infrared spectroscopy) and PLS-DA (partial least squares discriminant analysis) was developed. A hierarchical strategy of sequential modeling was performed with PLS-DA. The main model discriminated four classes: 5-MeO-MIPT, methylenedioxyamphetamines (MDMA and MDA), methamphetamine, and cathinones. Two submodels were built to identify drugs present in MDs and cathinones classes. Models were validated through the estimate of figures of merit. The average reliability rate (RLR) of the main model was 96.8% and accordance (ACC) was 100%. For the submodels, RLR and ACC were 100%. The reliability of the models was corroborated through their spectral interpretation. Thus, spectral assignments were performed by associating informative vectors of each specific modeled class to the respective drugs. The developed method is simple, fast, and can be applied to the forensic laboratory routine, leading to objective results reports useful for forensic scientists and law enforcement.


Assuntos
Drogas Desenhadas/química , Drogas Ilícitas/química , Psicotrópicos/isolamento & purificação , Análise Discriminante , Toxicologia Forense/métodos , Humanos , Análise dos Mínimos Quadrados , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos
4.
Forensic Sci Int ; 283: e8-e12, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29295746

RESUMO

MDMA and sildenafil are two examples among many substances consumed in "raves", as well as in other types of "recreative" social events nowadays. During the first six months of 2017, five cases of supposedly MDMA tablets seized by local law enforcement forces in the state of Minas Gerais, Brazil, and brought to our forensic laboratory for examination, attracted our attention among dozens of others, as the tablets apprehended in these cases were, in fact, colorfully painted versions of genuine, pentagon-shaped, sildenafil tablets, freely available for sale in local pharmacies and drugstores. Physical profiling, together with ATR-FTIR spectral matching, multi-component/deconvolution analysis and correlation were employed to prove that these tablets were genuine sildenafil tablets from a specific manufacturer, painted in a colorful way so that they could be marketed as MDMA tablets to unsuspecting buyers.

5.
Sci Justice ; 57(4): 283-295, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28606335

RESUMO

Viagra and Cialis are among the most counterfeited medicines in many parts of the world, including Brazil. Despite the many studies that have been made regarding discrimination between genuine and counterfeit samples, most published works do not contemplate generic and similar versions of these medicines and also do not explore excipients/adjuvants contributions when characterizing genuine and suspected samples. In this study, we present our findings in exploring ATR-FTIR spectral profiles for characterizing both genuine and questioned samples of several generic and brand-name sildenafil- and tadalafil-based tablets available on the Brazilian market, including Viagra and Cialis. Multi-component spectral matching (deconvolution), objective visual comparison and correlation tests were used during analysis. Besides from allowing simple and quick identification of counterfeits, results obtained evidenced the strong spectral similarities between generic and brand-named tablets employing the same active ingredient and the indistinguishability between samples produced by the same manufacturer, generic or not. For all sildenafil-based and some tadalafil-based tablets tested, differentiation between samples from different manufacturers, attributed to slight variations in excipients/adjuvants proportions, was achieved, thus allowing the possibility of tracing an unknown/unidentified tablet back to a specific manufacturer.


Assuntos
Medicamentos Falsificados , Medicamentos Genéricos , Citrato de Sildenafila/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier , Tadalafila/síntese química , Brasil , Humanos
6.
Forensic Sci Int ; 275: 302-307, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28445860

RESUMO

At the beginning of 2015, sixty-two capsules containing red-brown crystals seized in a historical city in Brazil were sent to this forensic laboratory for drug testing analysis. The material was identified as being Brephedrone, a new psychoactive substance and a bromine synthetic cathinone that is related to serotonin transportation. This substance was analyzed by ATR-FTIR, GC-MS, LC-MS, 1H, 13C and 2D NMR. Brephedrone apprehensions have been previously reported in Finland, France and Spain. It was the first detection of this substance in the State of Minas Gerais. No reports or information regarding any other apprehension nor identification of Brephedrone in Brazil were known prior to the present case.


Assuntos
Drogas Desenhadas/química , Psicotrópicos/química , Brasil , Cromatografia Líquida , Tráfico de Drogas , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Explore (NY) ; 11(6): 455-60, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26520228

RESUMO

BACKGROUND: Water is a key ingredient in the creation and sustainment of life. Moreover, water may be a key vehicle in the processes of energy healing, such as in the preparation of homeopathic remedies and spiritual treatments. Given these properties, the purpose of this study was to investigate whether the application of Johrei to water could lead to significant changes in the hydrodynamic behaviour of the fluid. METHODS: Four regular Johrei practitioners (P1, P2, P3 and P4) were selected for this study. Dripping water produced at the tip of a capillary was used as the hydrodynamic behaviour model. This behaviour was modelled mathematically, and tuning parameters φ4 and τ were used to assess significant differences in the dripping water samples that were subjected to Johrei compared with the samples that were not so treated. The tuning parameters were obtained using the Levenberg-Marquardt fitting algorithm. The data sets for each Johrei practitioner and the control experiment were analysed using ANOVA and a paired t-test. RESULTS: The mathematical model exhibited an excellent fit to our data, generating correlation coefficients (r) greater than or equal to 0.999. Significant differences were observed in both τ (P1 and P2, P < 0.05 and P < 0.01, respectively) and φ4 (P2, P < 0.01). As expected, no significant difference for the control experiment (without Johrei) was observed. CONCLUSIONS: Our results indicated a statistically significant change in the hydrodynamic behaviour of water correlated with Johrei treatment for 50% of the participating Johrei practitioners.


Assuntos
Hidrodinâmica , Cura Mental , Água , Humanos , Projetos Piloto
8.
Explore (NY) ; 6(5): 313-23, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20832764

RESUMO

The effect of Johrei treatment on the crystallization of sucrose from supersaturated solutions was studied in comparison with the crystallization in untreated solutions. This work was performed assuming that Johrei enhances the natural mechanisms of equilibrium restoration in biological and nonbiological systems. The crystallization in Johrei-treated solutions as judged by statistical analysis was found to be faster than the crystallization in untreated solutions. A discussion is presented about the mechanisms possibly involved.


Assuntos
Terapias Complementares/métodos , Cristalização , Sacarose/química , Soluções
9.
Philos Trans A Math Phys Eng Sci ; 366(1864): 319-28, 2008 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-17673414

RESUMO

The motility of living eukaryotic cells is a complex process driven mainly by polymerization and depolymerization of actin filaments underneath the plasmatic membrane (actin cytoskeleton). However, the exact mechanisms through which cells are able to control and employ 'actin-generated' mechanical forces, in order to change shape and move in a well-organized and coordinated way, are not quite established. Here, we summarize the experimental results obtained by our research group during recent years in studying the motion of living cells, such as macrophages and erythrocytes. By using our recently developed defocusing microscopy technique, which allows quantitative analysis of membrane surface dynamics of living cells using a simple bright-field optical microscope, we were able to analyse morphological and dynamical parameters of membrane ruffles and small membrane fluctuations, study the process of phagocytosis and also measure values for cell refractive index, membrane bending modulus and cell viscosity. Although many questions still remain unanswered, our data seem to corroborate some aspects of recent physical models of cell membranes and motility.


Assuntos
Membrana Celular/fisiologia , Movimento Celular/fisiologia , Animais , Eritrócitos/fisiologia , Eritrócitos/ultraestrutura , Humanos , Macrófagos/fisiologia , Macrófagos/ultraestrutura , Fagocitose/fisiologia
10.
Biophys J ; 91(3): 1108-15, 2006 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16617074

RESUMO

Defocusing microscopy (DM) is a recently developed technique that allows quantitative analysis of membrane surface dynamics of living cells using a simple bright-field optical microscope. According to DM, the contrast of defocused images is proportional to cell surface curvature. Although, until now, this technique was used mainly to determine size and amount of membrane shape fluctuations, such as ruffles and small random membrane fluctuations, in macrophages, its applications on cell biology extend beyond that. We show how DM can be used to measure optical and mechanical properties of a living macrophage, such as cell refractive index n, membrane bending modulus K(c), and effective cell viscosity eta for membrane-actin meshwork relaxation. Experimental data collected from defocused images of bone marrow-derived macrophages were used to evaluate these parameters. The obtained values, averaged over several different macrophages, are n = (1.384 +/- 0.015), K(c) approximately 3.2 x 10(-19) J, and eta approximately 459 Pa.s. We also estimate the amplitude of the small fluctuations to be of the order of 3 nm, which is around the step size of a polymerizing actin filament.


Assuntos
Células da Medula Óssea/metabolismo , Membrana Celular/metabolismo , Macrófagos/metabolismo , Microscopia/métodos , Actinas/química , Animais , Processamento de Imagem Assistida por Computador , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Microscopia/instrumentação , Modelos Estatísticos , Distribuição Normal , Fatores de Tempo
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