FF - Faculdade de Farmácia
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Navegando FF - Faculdade de Farmácia por Por Orientador "Bozinis, Marize Campos Valadares"
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Item Avaliação farmacológica e toxicológica de novos candidatos a protótipos de fármacos antitumorais(Universidade Federal de Goiás, 2011-03-02) Carvalho, Flávio Silva de; Menegatti, Ricardo; Bozinis, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018; Cunha, Luiz Carlos da; Lião, Luciano MoraisAs part of a line of research aimed at the pharmacological and toxicological evaluation of new candidates for antitumor drug prototypes, this work was conducted to evaluate pharmacological and toxicological compounds LQFM030, and LQFM031 LQFL032, drawn from nutlins prototypes. Additionally, we also evaluated whether the compounds LQFM004, LQFM005, and LQFM028 LQFM029 initially envisioned as candidates for prototypes of antipsychotic drugs, drawn from LASSBio579. Initially there was a cytotoxic screening all candidates, using the cytotoxicity test of exclusion of Trypan Blue in K-562 cells. Given this, it was observed that the best IC50 values were obtained with the candidates and LQFM030 LQFM029 (0.55 and 0.56 mM, respectively) and from then on had as starting point for these two molecules to a more detailed and thorough cytotoxicity, where it was observed that the molecule had the best LQFM030 cytotoxic profile in the test of exclusion of Trypan blue and the MTT reduction test, at intervals of 24, 48 and 72, compared with LQFM029 the molecule, using the cell line K-562. Given this, the candidate LQFM030 was the target of other studies conducted to study the survival, safety tests (Capture the Neutral Red dye, Acute Toxicity Oral), cell cycle, cell death mechanism of apoptosis and antioxidant activity. The data showed that the molecule LQFM030 increased life expectancy of the animals, and an IC50 value commensurate with the value of Nutlins found in literature, on the evaluation of acute toxicity, according to OECD 423, the molecule was rated 5 or non- classified according to the classification GSH, the cell cycle was observed an increase in G2 / M phase (73%) and sub-G1 phase (73.6%), and a decrease in S phase (40.9%) ; to assess the mechanism of cell death was characterized increased expression of Bax (8 times compared to untreated group), and a decrease of Bcl-2 (84%) as well as an increase in membrane potential and a decrease of ROS (reactive oxygen species), where there was not a change in protein expression of TNF and NFκβ; antioxidant activity did not show a significant effect, and before the candidate cyclic voltammetry showed only the presence of peak oxidation, not being characterized as a good redox system. When tested for safety in basal cell 3T3, the candidate presented a cytotoxicity with IC50 value of approximately 0.14 mM Thus, the candidate prototype antitumor drug LQFM030 presented as a good candidate for antitumor prototype with important data for such purpose, and the need for further detailed studies to better conceptualization.Item Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018(Universidade Federal de Goiás, 2011-08-31) Costa, Fabiana Bettanin; Bozinis, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018; Bozinis, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018; Blanco, Marcos Luengo; Cruz, Andrezza Furquim daCancer is a serious public health problem not only in Brazil but worldwide. Among the various types of cancer known, leukemia is a one of high incidence. In this context, our study aimed to verify the citotoxicity of the compound LQFM-018, in leukemic cells. Both the method of trypan blue exclusion as in the MTT, it was observed a concentration and time dependent response after treatment with the compound LQFM-018. The cell death mechanism was assessed by flow cytometry. The cell cycle analysis showed a decrease of cells in G1 phase with a consequent increase in S phase and G2 / M. The cell death mechanism detected by annexin-V test showed that the K-562 cells were mainly in necrosis. The increased release of LDH also corroborated with the necrotic process. In the treated cells, there was not a significant expression of tumor suppressor protein p-53. The expression of nuclear factor кB increased and decreased expression of ROS. It was also found an increased expression of TNF-R1 receptor, cytochrome-c, decreased ΔΨm and not the expression of proteins Bax and Bcl-2. Acute oral toxicity test was done in vivo. According to the results, the compound LQFM-018 was classified as category 5. The statistical analysis was done using Student t test and ANOVA followed or not by Bonferroni post-test. Was considered statistically significant p<0.05. From these results, we found that the compound LQFM-018 presents potential antitumor activity, but other tests are needed to confirm these results.Item Avaliação da atividade citotóxica e indutora de apoptose da grandisina em células leucêmicas K-562 com fenótipo de resistência a fármacos(Universidade Federal de Goiás, 2009-11-03) Menezes, Elizabeth Gomes Paulino; Bozinis, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018; Bozinis, Marize Campos Valadares; Pessoa, Cláudia de Ó; Ribeiro, ElisângelaIn this study the antileukemic potential of grandisin, a neolignan extracted from Piper solmsianum, was investigated against K-562 lymphocytic genealogy, which demonstrates a phenotype of resistance to new drugs. The cytotoxicity of grandisin (0.018 to 2.365 μMol) was evaluated in K-562 and in normal peripheral blood lymphocytes by using Blue of Trypan and MTT({[3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] bromide}) methods. In the cytotoxic activity research about grandisin on K-562 cells and lymphocytes during 24 hours by the Blue of Trypan method, the grandisin got IC50 (inhibitory concentration to fifty percent) of 1.075 and 0.375 μMol to lymphocytes and K-562, respectively. After 48 hours, the cytotoxicity in normal cells remained themselves and we noticed there was an increase in IC50 leukemic cells of 0.198 μMol and 0.200 μMol in K-562 and lymphocytes, respectively. For the MTT test, results were similar to those found during the previous experiment (IC50K-562 11,98 μMol IC50lymphocytes 0,425 μMol for a period of 24 hours and IC50K-562 0,685 IC50lymphocytes 0,851 μMol for a period of 48 hours). The research about cell death mechanisms showed the treatment in K-562 cells joined to 0.036 μMol of grandisin during 24 hours, induces to an increase of cells population in G1 stage of cell cycle and it also induces to a decline of cells population in G2 stage and S, respectively. These factors also indicate that the grandisin was induced to a cell cycle standstill in G1 stage, which is proportionated to the most antileukemic agents existing. Cell death with apoptosis signs was showed by the research about these cells morphology. Moreover, the treatment of leukemic cells with 0.072, 0.036, 0.018 μMol of grandisin during 24 hours has promoted exposure of annexin V, wich is a first indicator of apoptosis. In these cells, the activity research of 3, 6 and 9 caspases and cell death mediators Bcl2 and Bax showed that cell death happens in dependent-caspase way and with balance induction between Bcl2 and Bax. Collectively, these results introduce a new model able to induce apoptosis in a leukemic cell genealogy with important features of resistance to the process of programmed cell death.