DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item A chloroquinoline derivate presents effective in vitro and in vivo antileishmanial activity against Leishmania species that cause tegumentary and visceral leishmaniasis.(2019) Sousa, Jéssica Karine Távora de; Antinarelli, Luciana Maria Ribeiro; Mendonça, Débora Vasconcelos Costa; Lage, Daniela Pagliara; Tavares, Grasiele de Sousa Vieira; Dias, Daniel Silva; Ribeiro, Patrícia Aparecida Fernandes; Ribeiro, Fernanda Ludolf; Coelho, Vinicio Tadeu da Silva; Silva, João Augusto Oliveira da; Melo, Luísa Helena Perin de; Oliveira, Bianka A.; Alvarenga, Denis Fernando; Chávez Fumagalli, Miguel Angel; Brandão, Geraldo Célio; Vandack, Nobre; Pereira, Guilherme Rocha; Coimbra, Elaine Soares; Coelho, Eduardo Antônio FerrazThe identification of new therapeutics to treat leishmaniasis is desirable, since available drugs are toxic and present high cost and/or poor availability. Therefore, the discovery of safer, more effective and selective pharmaceutical options is of utmost importance. Efforts towards the development of new candidates based on molecule analogs with known biological functions have been an interesting and cost-effective strategy. In this context, quinoline derivatives have proven to be effective biological activities against distinct diseases. In the present study, a new chloroquinoline derivate, AM1009, was in vitro tested against two Leishmania species that cause leishmaniasis. The present study analyzed the necessary inhibitory concentration to preclude 50% of the Leishmania promastigotes and axenic amastigotes (EC50 value), as well as the inhibitory concentrations to preclude 50% of the murine macrophages and human red blood cells (CC50 and RBC50 values, respectively). In addition, the treatment of infected macrophages and the inhibition of infection using pre-treated parasites were also investigated, as was the mechanism of action of the molecule in L. amazonensis. To investigate the in vivo therapeutic effect, BALB/c mice were infected with L. amazonensis and later treated with AM1009. Parasitological and immunological parameters were also evaluated. Clioquinol, a known antileishmanial quinoline derivate, and amphotericin B (AmpB), were used as molecule and drug controls, respectively. Results in both in vitro and in vivo experiments showed a better and more selective action of AM1009 to kill the in vitro parasites, as well as in treating infected mice, when compared to results obtained using clioquinol or AmpB. AM1009-treated animals presented significantly lower average lesion diameter and parasite burden in the infected tissue and organs evaluated in this study, as well as a more polarized antileishmanial Th1 immune response and low renal and hepatic toxicity. This result suggests that AM1009 should be considered a possible therapeutic target to be evaluated in future studies for treatment against leishmaniasis.Item Poloxamer 407 (Pluronic® F127)-based polymeric micelles for amphotericin B : in vitro biological activity, toxicity and in vivo therapeutic efficacy against murine tegumentary leishmaniasis.(2016) Mendonça, Débora Vasconcelos Costa; Lage, Letícia Martins dos Reis; Lage, Daniela Pagliara; Chávez Fumagalli, Miguel Angel; Ribeiro, Fernanda Ludolf; Roatt, Bruno Mendes; Souza, Daniel Menezes; Faraco, André Augusto Gomes; Castilho, Rachel Oliveira; Tavares, Carlos Alberto Pereira; Barichello, José Mario; Duarte, Mariana Costa; Coelho, Eduardo Antônio FerrazIn the present study, a Poloxamer 407-based amphotericin B (AmpB)-containing polymeric micelles system (AmpB/M) was employed in the treatment of Leishmania amazonensis-infected BALB/c mice. Initially, the in vitro antileishmanial activity (IC50 value) of AmpB/M and B-AmpB/M (empty micelles) against stationary promastigotes and amastigotes-like forms of the parasites was determined, and results were of 1.83 ± 0.4 and 22.1 ± 0.7 mM, respectively, for the promastigotes, and of 2.27 ± 0.5 and 33.98 ± 2.6 mM, respectively, for the amastigotes-like. The cytotoxic concentration (CC50) values of these products were also evaluated, and we found the results of 119.5 ± 9.6 and 134.7 ± 10.3 mM, respectively. With these values, the selectivity index (SI) was calculated and results were of 65.3 and 5.4, respectively, for the promastigotes, and of 59.3 and 3.96, respectively, for the amastigotes-like of the parasites. Free AmpB showed IC50 values of 1.2 ± 0.3 and 2.5 ± 0.5 mM for the promastigotes and amastigotes-like, respectively, whereas the CC50 value was of 9.5 ± 0.4 mM. The SI values of this drug were of 7.9 and 3.8, respectively, for the promastigote and amastigote-like stages of the parasites. After, animals were infected and received saline or were treated subcutaneously with free AmpB, AmpB/M or B-AmpB/M. In the results, free AmpB-treated and infected mice showed reductions in their body weight, which were associated with hepatic and renal damage; however, no organic alteration was observed in the AmpB/Mtreated animals. In addition, these animals showed significant reductions in their lesion average size and in the parasite burden in all evaluated infected tissue and organs, when compared to the other groups; as well as significantly higher levels of antileishmanial IFN-g, IL-12, GM-CSF and nitrite, which were associated with low production of IL-4, IL-10 and IgG1 isotype antibodies. In conclusion, this AmpB/M system could be considered as an alternative for future studies in the treatment of tegumentary leishmaniasis.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 Costa