Rômulo José Soares-Bezerra
Oswaldo Cruz Foundation
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Publication
Featured researches published by Rômulo José Soares-Bezerra.
Revista Brasileira De Ciencias Farmaceuticas | 2004
Rômulo José Soares-Bezerra; Leonor L. Leon; Marcelo Genestra
Leishmanioses sao doencas causadas por protozoarios do genero Leishmania sp., que se apresentam na forma promastigota ou amastigota; os promastigotas infectam o inseto vetor e os amastigotas sao as formas infectivas antes presentes em macrofagos humanos. O tratamento utilizado pela clinica tem se mostrado ineficaz; os farmacos utilizados se apresentam na forma injetavel, o que dificulta o tratamento, ja que o paciente, para ser tratado, deve ser internado para as aplicacoes - que sao dolorosas - e assim muitos pacientes desistem do tratamento. Outra razao para a internacao e a monitoracao dos efeitos colaterais causados pelos farmacos. Por estas razoes a quimioterapia para leishmaniose tem sido objeto de estudo de muitos laboratorios de pesquisa, os quais tem testado outras substâncias quimicas e extratos de plantas com a finalidade de se encontrar novos agentes leishmanicidas com menores efeitos colaterais e otima biodisponibilidade. Alem disso, pesquisam-se, tambem, outras formas farmaceuticas que viabilizem a aplicacao desses farmacos, o que tornaria desnecessaria a internacao do paciente para se efetuar o tratamento. Este artigo visa discutir os recentes avancos da quimioterapia utilizada para as leishmanioses e, tambem, apresentar os aspectos farmacologicos e bioquimicos da participacao de moleculas intracelulares do parasita como alvos de farmacos.
Cell Biochemistry and Function | 2008
Marcelo Genestra; Rômulo José Soares-Bezerra; Liliane Gomes‐Silva; Daniela L. Fabrino; Thiago Bellato‐Santos; Denise Barçante Castro-Pinto; Marilene M. Canto-Cavalheiro; Leonor L. Leon
Leishmania parasites survive despite exposure to the toxic nitrosative oxidants during phagocytosis by the host cell. In this work, the authors investigated comparatively the resistance of Leishmania amazonensis promastigotes and axenic amastigotes to a relatively strong nitrosating agent that acts as a nitric oxide (NO) donor, sodium nitroprusside (SNP). Results demonstrate that SNP is able to decrease, in vitro, the number of L. amazonensis promastigotes and axenic amastigotes in a dose‐dependent maner. Promastigotes, cultured in the presence of 0.25, 0.5, and 1 mmol L−1 SNP for 24 h showed about 75% growth inhibition, and 97–100% when the cultures were treated with >2 mmol L−1 SNP. In contrast, when axenic amastigotes were growing in the presence of 0.25–8 mM SNP added to the culture medium, 50% was the maximum of growth inhibition observed. Treated promastigotes presented reduced motility and became round in shape further confirming the leishmanicidal activity of SNP. On the other hand, axenic amastigotes, besides being much more resistant to SNP‐mediated cytotoxicity, did not show marked morphological alteration when incubated for 24 h, until 8 mM concentrations of this nitrosating agent were used. The cytotoxicity toward L. amazonensis was attenuated by reduced glutathione (GSH), supporting the view that SNP‐mediated toxicity triggered multiple oxidative mechanisms, including oxidation of thiols groups and metal‐independent oxidation of biomolecules to free radical intermediates. Copyright
Pharmaceuticals | 2013
Rômulo José Soares-Bezerra; Andrea Surrage Calheiros; Natiele Carla da Silva Ferreira; Valber da Silva Frutuoso; Luiz Anastacio Alves
Natural products have reemerged in traditional medicine as a potential source of new molecules or phytomedicines to help with health disorders. It has been established that members of the P2X subfamily, ATP-gated ion channels, are crucial to the inflammatory process and pain signalization. As such, several preclinical studies have demonstrated that P2X2R, P2X3R, P2X4R and P2X7R are promising pharmacological targets to control inflammatory and pain disorders. Several studies have indicated that natural products could be a good source of the new specific molecules needed for the treatment of diseases linked to inflammation and pain disorders through the regulation of these receptors. Herein, we discuss and give an overview of the applicability of natural products as a source to obtain P2X receptors (P2XR) selective antagonists for use in clinical treatment, which require further investigation.
Journal of Enzyme Inhibition and Medicinal Chemistry | 2008
Rômulo José Soares-Bezerra; Edson F. da Silva; Aurea Echevarria; Liliane Gomes-da-Silva; Léa Cysne-Finkelstein; Fabiane Pereira Monteiro; Leonor L. Leon; Marcelo Genestra
l-arginine is involved in the production of both nitric oxide (NO), mediated by nitric oxide synthase (NOS) and l-ornithine, by arginase activity. It is generally accepted that NO regulation occurs mainly at the transcriptional level of NOS. In a previous work we purported that there is evidence that Leishmania sp. can produce NO from l-arginine. An arginase activity in its gene sequence has also been reported in Leishmania parasites. In a search for intracellular targets as potential antileishmanicidal agents, such as the l-arginine metabolism, we used 1,3,4-thiadiazolium mesoionic compounds, that have been demonstrated to be cytotoxic to the Leishmania amazonensis, when compared to Pentamidine isethionate as a reference drug. Parasites were assayed in absence/presence of 4′- and 3′- methoxy mesoionic derivatives in order to verify the effect on NO production and arginase activity in L. amazonensis. The results indicated that the drugs reduce from 70 to 90% of the NO production by the parasite and act on a soluble nitric oxide synthase purified from L. amazonensis promastigotes and axenic amastigotes.
PLOS ONE | 2015
Rômulo José Soares-Bezerra; Natiele Carla da Silva Ferreira; Anael Viana Pinto Alberto; André Gustavo Calvano Bonavita; Antonio Augusto Fidalgo-Neto; Andrea Surrage Calheiros; Valber da Silva Frutuoso; Luiz Anastacio Alves
ATP physiologically activates the P2X7 receptor (P2X7R), a member of the P2X ionotropic receptor family. When activated by high concentrations of ATP (i.e., at inflammation sites), this receptor is capable of forming a pore that allows molecules of up to 900 Da to pass through. This receptor is upregulated in several diseases, particularly leukemia, rheumatoid arthritis and Alzheimers disease. A selective antagonist of this receptor could be useful in the treatment of P2X7R activation-related diseases. In the present study, we have evaluated several parameters using in vitro protocols to validate a high-throughput screening (HTS) method to identify P2X7R antagonists. We generated dose-response curves to determine the EC50 value of the known agonist ATP and the ICs50 values for the known antagonists Brilliant Blue G (BBG) and oxidized ATP (OATP). The values obtained were consistent with those found in the literature (0.7 ± 0.07 mM, 1.3-2.6 mM and 173-285 μM for ATP, BBG and OATP, respectively). The Z-factor, an important statistical tool that can be used to validate the robustness and suitability of an HTS assay, was 0.635 for PI uptake and 0.867 for LY uptake. No inter-operator variation was observed, and the results obtained using our improved method were reproducible. Our data indicate that our assay is suitable for the selective and reliable evaluation of P2X7 activity in multiwell plates using spectrophotometry-based methodology. This method might improve the high-throughput screening of conventional chemical or natural product libraries for possible candidate P2X7R antagonist or agonist
Experimental Parasitology | 2013
Rômulo José Soares-Bezerra; Leonor L. Leon; Aurea Echevarria; Camilla Moretto dos Reis; Liliane Gomes‐Silva; Carla G. Agostinho; Renan A. Fernandes; Marilene M. Canto-Cavalheiro; Marcelo Genestra
Leishmaniasis is a spectrum of infectious diseases caused by Leishmania protozoan parasites. The purpose of this study was to perform, in vitro, a comparative analysis of the activity amastigotes. Results showed excellent efficacy of all compounds against axenic amastigotes, compared to pentamidine isethionate, the reference drug used. The cytotoxic effect of these mesoionic compounds of six mesoionic compounds (three 1,3,4-thiadiazolium-2-aminide and three 1,2,3-oxadiazolium-5-olate class compounds) was evaluated in mouse peritoneal macrophages using MTT assay, low toxicity (≈ 10%) for these mammalian cells being observed. In an attempt to define a potential drug target, the activities of nitric oxide synthase (NOS) and arginase of the parasites treated with the mesoionic derivatives were evaluated. NOS was purified from a cell-free extract of infective promastigotes and axenic amastigotes and all derivatives tested were able to inhibit the enzyme as monitored by the decrease of NADPH consumption. Arginase activity from both stages of the parasite was measured using urea production and none of the compounds inhibited the enzyme activity of axenic amastigotes. However, the compounds without substituents (MI-H and SID-H) were able to inhibit arginase activity of these parasites.
International journal of food science | 2016
Leonardo G. Ferreira; Robson Xavier Faria; Natiele Carla da Silva Ferreira; Rômulo José Soares-Bezerra
Dyes were first obtained from the extraction of plant sources in the Neolithic period to produce dyed clothes. At the beginning of the 19th century, synthetic dyes were produced to color clothes on a large scale. Other applications for synthetic dyes include the pharmaceutical and food industries, which are important interference factors in our lives and health. Herein, we analyzed the possible implications of some dyes that are already described as antagonists of purinergic receptors, including special Brilliant Blue G and its derivative FD&C Blue No. 1. Purinergic receptor family is widely expressed in the body and is critical to relate to much cellular homeostasis maintenance as well as inflammation and cell death. In this review, we discuss previous studies and show purinergic signaling as an important issue to be aware of in food additives development and their correlations with the physiological functions.
PLOS ONE | 2015
Rômulo José Soares-Bezerra; Natiele Carla da Silva Ferreira; Anael Viana Pinto Alberto; André Gustavo Bonavita; Antonio Augusto Fidalgo-Neto; Andrea Surrage Calheiros; Valber da Silva Frutuoso; Luiz Anastacio Alves
There are errors in the seventh sentence of the Abstract. Specifically, the values provided for ATP, BBG and OATP are incorrect. The correct sentence is: The values obtained were consistent with those found in the literature (0.7 ± 0.07 mM, 1.3–2.6 μM and 173–285 μM for ATP, BBG and OATP, respectively). Additionally, there are errors in the units of Table 1. The correct units for columns BBG (IC50) and OATP (IC50) are μM. Please see the corrected Table 1 here. Table 1 IC50 or EC50 values for P2X7R agonists or antagonists using different methods.
Archive | 2018
Natiele Carla da Silva Ferreira; Rômulo José Soares-Bezerra; Rebeca Ferreira Couto da Silveira; Clayton Menezes da Silva; Carla Santos de Oliveira; Andrea Surrage; Tânia M. A. Alves; Carlos L. Zani; Luiz Anastacio Alves
P2Y2 and P2Y4 receptors are physiologically activated by UTP and are widely expressed in many cell types in humans. They promote an increase in intracellular calcium via PLCβ/ IP3 and act on ion flux and water secretion. P2Y2 plays an important role in inflammation and proliferation of tumor cells, which could be attenuated with the use of antagonists. However, little is known about the physiological functions related to P2Y4 due to the lack of selective ligands for these receptors, which can be solved through the search of novel compounds with antagonistic activity. In the present study, we have applied a methodology of calcium measurement to identify new antagonist candidates for these receptors. Firstly, we established optimal conditions for calcium assay using J774.G8, a murine macrophage cell line, which expresses functional P2Y2 and P2Y4 receptors. J774.G8 cells were loaded with 2 μM of Fluo-4 to test its sensitivity in responding calcium stimuli. ATP and ionomycin, known as inductors of intracellular calcium rise, were used to stimulate cells. The EC50 obtained were 11 μM and 103 nM, respectively. Subsequently, investigation of P2Y2 and P2Y4 expression was performed. These cells responded with EC50 of 1.021 μM to the UTP stimulation. Screening assays were performed and a total of 100 extracts from Brazilian natural products were tested. JA2, RA3, and RB3 extracts stood out for their ability to inhibit UTP-induced responses without causing cytotoxicity and presented IC50 of 32.32 μg/mL, 14.99 μg/mL, and 12.98 μg/mL, respectively. Collectively, our results point to the discovery of potential antagonists candidates from natural products for UTPactivated receptors.
Archives of Medical Research | 2006
Marcelo Genestra; Damiana Guedes-Silva; Wilson Jacinto Silva de Souza; Léa Cysne-Finkelstein; Rômulo José Soares-Bezerra; Fabiane Pereira Monteiro; Leonor L. Leon