DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item Synthesis of novel papulacandin D analogs and evaluation of their antifungal potential.(2020) Bretas, Ana Carolina Oliveira; Souza, Thiago Belarmino de; Borelli, Beatriz; Johan, Suzana; Alves, Ricardo JoséSystemic fungal infections are a growing problem in contemporary medicine and few drugs are licensed for therapy of invasive fungal infections. Differences between fungi and humans, like the presence of a cell wall in fungal cells, can be explored for designing new drugs. (1,3)-β-D-glucan synthase, an enzyme that catalyzes the synthesis of (1,3)-β-D-glucan, a structural and essential component of the fungal cell wall, is absent in mammals and this makes it an excellent target for the development of new antifungal agents. Papulacandins are a family of natural antifungal agents targeting (1,3)-β-D-glucan synthase. In this study we describe the synthesis and biological evaluation of two new Papulacandin analogs as potential (1,3)-β-D-glucan synthase inhibitors.Item Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system.(2016) Duarte, Mariana Costa; Lage, Letícia Martins dos Reis; Lage, Daniela Pagliara; Martins, Vivian Tamietti; Carvalho, Ana Maria Ravena Severino; Roatt, Bruno Mendes; Souza, Daniel Menezes; Tavares, Carlos Alberto Pereira; Alves, Ricardo José; Barichello, José Mario; Coelho, Eduardo Antônio FerrazNewtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered, as well as the evaluation of new molecules that have already shown to present biological activity. In this context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline (8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load. The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines, as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1 isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion, 8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined with other drugs, as an alternative treatment for VL.Item An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis.(2016) Lage, Letícia Martins dos Reis; Barichello, José Mario; Lage, Daniela Pagliara; Mendonça, Débora Vasconcelos Costa; Carvalho, Ana Maria Ravena Severino; Rodrigues, Marcella Rezende; Souza, Daniel Menezes; Roatt, Bruno Mendes; Alves, Ricardo José; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antônio Ferraz; Duarte, Mariana CostaItem Splenectomy increases mortality in murine Trypanosoma cruzi infection.(2011) Maioli, Tatiani Uceli; Assis, Frankcinéia Aparecida de; Vieira, Paula Melo de Abreu; Borelli, Primavera; Santiago, Helton da Costa; Alves, Ricardo José; Romanha, Alvaro José; Carneiro, Cláudia Martins; Faria, Ana Maria Caetano deThe spleen is a secondary lymphoid organ that harbours a variety of cells such as T and B lymphocytes and antigen-presenting cells important to immune response development. In this study, we evaluated the impact of spleen removal in the immune response to experimental Trypanosoma cruzi infection. C57BL/6 mice were infected with Y strain of the parasite and infection was followed daily. Mice that underwent splenectomy had fewer parasites in peripheral blood at the peak of infection; however, mortality was increased. Histological analysis of heart and liver tissues revealed an increased number of parasites and inflammatory infiltrates at these sites. Spleen removal was associated with reduction in IFN-γ and TNF-α production during infection as well as with a decrease in specific antibody secretion. Haematological disorders were also detected. Splenectomized mice exhibited severe anaemia and decreased bone marrow cell numbers. Our results indicate that spleen integrity is critical in T. cruzi infection for the immune response against the parasite, as well as for the control of bone marrow haematological function.