Orientador: Claudia Bincoletto Trindade / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T18:43:42Z (GMT). No. of bitstreams: 1 Smith_MickaelaCardosoMartinez_M.pdf: 1162038 bytes, checksum: 0483ed1cd125191349f265a1bc585185 (MD5) Previous issue date: 2006 / Resumo: Estudos experimentais envolvendo a caracterização fármaco-toxicológica de novos fármacos são de grande importância na pesquisa inicial sobre drogas (ERDAL et al., 2005). Sendo assim, neste projeto um dos nossos objetivos iniciais foi avaliar os possíveis efeitos antineoplásicos de uma nova classe de drogas organometálicas contendo paládio como metal de transição, denominada paladaciclo ferroceno 1:2, utilizando para isto, a linhagem de células leucêmica K562 (leucemia mielóide crônica) e Jurkat (leucemia linfóide aguda). Os valores de IC50% obtidos na linhagem K562 após 72 horas de tratamento com o composto paladaciclo foram 4,1 e 2,9 µM, nos testes de redução do MTT e exclusão por azul de trypan, respectivamente. Através da fragmentação de DNA observamos que o composto foi capaz de induzir apoptose nas células K562 e Jurkat. Aspectos morfológicos de apoptose nestas células também foram confirmados através da coloração de acredine orange visualizadas em microscopia de fluorescência nas células K562. Utilizando acredine orange, um corante que tem a característica de se acumular principalmente em lisossomas secundários de células tumorais, nós também analisamos o mecanismo bioquímico envolvido no processo de morte celular das células K562 induzidas pelo composto paladaciclo. Nossos resultados demonstraram que a expressão dos genes envolvidos no controle da apoptose (Bcl-2 e Bax) em ambas as linhagens celulares tratadas com o paladaciclo é similar ao controle sem tratamento. Por outro lado, o composto em estudo (6,0 µM) induziu a permeabilização da membrana lisossomal de células K562 após 5 horas de tratamento com ativação das caspases efetoras da apoptose 3 e 6. Este processo de ativação das caspases também foi observado após 72 horas de incubação com o paladaciclo. Como a catepsina B está abundantemente presente nos lisossomoas e sua liberação para o citosol é esperada após alterações da permeabilidade da membrana lisossomal, investigamos também a ativação de ambas as caspases, descritas acima, após a incubação das células K562 com um inibidor de catepsina B (CA074) por 2 horas antes da exposição ao paladaciclo (6,0 µM). Este estudo forneceu um resultado bastante interessante, pois demonstrou que a ativação das caspases efetoras da morte celular programada foi prevenida, sugerindo assim que a catepsina B está fortemente associada ao processo apoptótico em células K562. Sendo assim, podemos sugerir que o composto paladaciclo apresenta potencial antileucêmico, merecendo estudos adicionais que comprovem sua eficácia terapêutica / Abstract: Experimental studies involving the pharmaco-toxicogical properties of new drugs are of very importance in its initial development (ERDAL et al., 2005). In this study it was evaluated the possible antileukemic effects of a new organometallic class of drugs called palladacycle ferrocene 1:2, using the K562 and Jurkat leukaemia cell lines. The cell death mechanism of cytotoxicity induced by the Biphosphinic Palladacycle Complex (BPC) was studied using a K562 leukaemia cell line. The IC50% values obtained for K562 cells post 72 h of BPC were less than 5.0 µM by using MTT and trypan blue assays. Complex triggers apoptosis in K562 and Jurkat cells, inducing DNA fragmentation, as analysed through electrophoresis. Using the Acridine Orange (AO) vital staining combining fluorescence microscopy it was confirmed the presence these process in K562 cells. Lysosomal membrane permeabilization was also observed in K562 cells post 5 h of BPC, which suggests intralysossomal accumulation by proton-trapping, previous study, revealed that its pKa value ranged from 5.1 to 6.5. Caspase-3, and -6 activity induced by BPC in K562 cells was prevented by the cathepsin B inhibitor (CA-074). These events occurred in the presence of endogenous Bcl-2 and Bax expression. Taken together, these data suggest a novel lysosomal pathway for BPCinduced apoptosis, in which lysosomes are the primary target and cathepsin B acts as death mediator / Mestrado / Farmacologia / Mestre em Farmacologia

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-02-16T10:45:53Z No. of bitstreams: 2 Tese - Alexandre Pereira dos Santos - 2013.pdf: 10518696 bytes, checksum: 65112aa6a70b7f40682b3e2693fb2c76 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-02-16T10:46:16Z (GMT) No. of bitstreams: 2 Tese - Alexandre Pereira dos Santos - 2013.pdf: 10518696 bytes, checksum: 65112aa6a70b7f40682b3e2693fb2c76 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-02-16T10:46:16Z (GMT). No. of bitstreams: 2 Tese - Alexandre Pereira dos Santos - 2013.pdf: 10518696 bytes, checksum: 65112aa6a70b7f40682b3e2693fb2c76 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2013-05-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / For many centuries the plants are supplied raw material to produce an armory of therapeutic agents, either by synthesis or from metabolites of their own use. In this context especially species of the Cerrado region. A new species of Clusia still unidentified (Clusia sp) in endemic regions of Goiânia and Chapada dos Veadeiros has been popularly employed as antirheumatic agent, purgative, febrifuge, stomach problems as described for other species of the genus, and its application as anticancer agent . The number of studies confirming the application of this kind for cancer treatment is scarce justifying this work. we evaluated the potential antileucêmico in vitro and in vivo antitumor floral resin and latex obtained from the fruits of Clusia sp. Investigated and elucidated the possible mechanisms of action of these products on cell death and toxicity. Cytotoxicity screening performed on these samples K562, Lucena, HL-60, B16F10, PC3 and lymphocytes. Analyzed cell morphology after treatment of K562 cells with the resin and latex; evaluated the increased survival of animals after treatment with plant samples, estimated acute oral toxicity of resin and latex Clusia sp from cells of basal metabolism 3T3, investigated the potential hemolytic and immunosuppressive these vegetables samples. The results obtained from the tests carried out show interesting cytotoxic action in leukemia cells with IC50 values at 24, 48 and 72 hours resin 62,2, 31,1 and 5,09 µg/ml for the latex and 37,4; 14,5, and 8,58 µg/mL, respectively. Compared with the drugs used in therapy, such as Imatinib was not statistically significant difference between latex and imatinib mesylate, a drug used as reference in the treatment of leukemia. From the tests morphology with Giemsa or Hoechst was observed that both samples vegetables induced morphological changes typical of cell death in apoptosis. After treatment with the resin (62,2 µg/mL) and latex (37,4 µg/mL) was observed chromatin condensation, DNA fragmentation from the formation of apoptotic bodies, among other events that attest to cell death. In an attempt to elucidate the mechanism of death by flow cytometry was observed after treatment with the the resin and latex, externalization of phosphatidylserine, inducing the formation of reactive oxygen species, activation of caspases -3, -8 and -9, reducing mitochondrial membrane potential, release of cytochrome c, activation of Bax, all these processes involved in cell death. Increased survival in tumor-bearing animals were observed at doses of 125 mg/kg of resin and 250 mg/kg latex, higher doses were toxic. From the results of the estimated DL50 vegetable samples were classified in category 3 of the GHS. Immunosuppressive effect was observed for the resin and latex and moderate hemolytic was observed only for the resin. Given the above samples resin and latex Clusia sp exhibit interesting profile for the development of anticancer drugs. / Por muitos séculos as plantas têm fornecido matéria-prima para a produção de um arsenal de agentes terapêuticos, seja por síntese a partir de metabólitos ou de seu próprio uso. Nesse contexto destaque para espécies da região do Cerrado. Uma nova espécie de Clusia ainda não identificada (Clusia sp) endêmica nas regiões de Goiânia e Chapada dos Veadeiros tem sido empregada popularmente como agente antirreumático, purgativo, febrífugo, problemas estomacais como descrito para outras espécies do gênero, além de sua aplicação como agente anticancerígeno. O número de estudos confirmando a aplicação dessa espécie para o tratamento do câncer é escasso justificando realização deste trabalho. Para tal, foi avaliado o potencial antileucêmico in vitro e antitumoral in vivo da resina floral e látex obtidos dos frutos de Clusia sp. Investigado e elucidado os possíveis mecanismos de ação destes produtos sobre a morte celular e toxicidade. Realizada uma triagem de citotoxicidade destas amostras sobre células K562, Lucena, HL-60, B16F10, PC3 e linfócitos. Analisada a morfologia celular das células k562 após tratamento com a resina floral e o látex; avaliado o aumento da sobrevida de animais portadores de tumor após tratamento com as amostras vegetais, estimada a toxicidade aguda oral da resina e látex de Clusia sp a partir de células do metabolismo basal 3T3, investigado o potencial hemolítico e imunossupressor destas amostras vegetais. Os resultados obtidos a partir dos ensaios realizados apontam interessante ação citotóxica em células leucêmicas com valores de IC50 nos tempos de 24, 48 e 72 horas para a resina de 62,2; 31,1 e 5,09 µg/mL e para o látex de 37,4; 14,5 e 8,58 µg/mL, respectivamente. Em comparação com os fármacos empregados na terapêutica, como o Imatinibe não foi observada diferença estatística significativa entre o látex e o mesilato de imatinibe, fármaco empregado como referência no tratamento da leucemia. A partir dos ensaios de morfologia empregando os corantes de Giemsa e Hoechst foi possível observar que ambas as amostras vegetais induziram alterações morfológicas típicas de morte celular como a apoptose. Após o tratamento com a resina (62,2 µg/mL) e látex (37,4 µg/mL) foi observado condensação da cromatina, fragmentação do DNA a partir da formação de corpos apoptóticos, entre outros eventos qcue atestam a morte celular. Na tentativa de elucidar o mecanismo de morte por citometria de fluxo foi observado após tratamento com o a resina e látex, a externalização da fosfatidilserina, indução na formação de espécies reativas de oxigênio, ativação das caspases -3,-8 e -9, redução do potencial da membrana mitocondrial, liberação de citocromo c, ativação de Bax, todos esses processos envolvidos na morte celular. Aumento da sobrevida em animais portadores de tumor foi observada nas doses de 125 mg/kg para resina e de 250 mg/kg para o látex, doses superiores foram tóxicas. A partir dos resultados da estimativa da DL50 as amostras vegetais foram classificadas na categoria 3 do sistema GHS. Efeito imunossupressor foi observado para a resina e látex e ação hemolítica moderada foi observada apenas para a resina. Diante do exposto as amostras de resina e látex de Clusia sp apresentam interessante perfil para o desenvolvimento de fármacos antitumorais.

No description available.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-01-17T14:43:31Z No. of bitstreams: 2 Dissertação - Thaís Rosa Marques dos Santos - 2016.pdf: 1811805 bytes, checksum: 381d90956275aee309bb1d2948f724de (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-01-17T14:43:57Z (GMT) No. of bitstreams: 2 Dissertação - Thaís Rosa Marques dos Santos - 2016.pdf: 1811805 bytes, checksum: 381d90956275aee309bb1d2948f724de (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-01-17T14:43:57Z (GMT). No. of bitstreams: 2 Dissertação - Thaís Rosa Marques dos Santos - 2016.pdf: 1811805 bytes, checksum: 381d90956275aee309bb1d2948f724de (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-05-20 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Although the efforts employed by scientific community to discover new anticancer therapies suitable to the increasing cancer incidence and multidrug resistance, its necessary to develop more selective and target driven drugs. Therefore, in this work we have done a screening with LQFM030 analogues, which is a Nutlin-1 analogue, aiming to evaluate their cytotoxic potential. Furthermore, we have evaluated the cytotoxicity, the morphological alterations and the cell death induction mechanisms of the compound LQFM166 in leukemia cell line K562. In parallel, we have investigated the security profile of the compound upon 3T3 basal cell line to estimate its LD50 and the Selectivity Index. The cytotoxicity assays included the tetrazolium salt (MTT) reduction and the Neutral Red Uptake assays, to assess the cytotoxicity of LQFM166 in K562 and 3T3 cell lines, respectively. The investigation of cell death induction mechanisms was carried out using flow cytometry, whereby we have evaluated the cells biochemistry parameters, including cell cycle progression, phosphatidylserine externalization, caspases 3/7, 8 and 9 activity, cytochrome c release from mitochondria, p21, p27, Bax, Bcl-2, cyclin-B1 and NFkB expression, using specific labeling for each assay. Data were analyzed by t test and the difference between control and treated groups averages was considered statistically significant when p<0,05. Regarding leukemia cell line K562, the compound LQFM166 was cytotoxic, showing a dose-time-dependent profile. Morphological alterations were observed after treatment with the compound at cellular and nuclear levels, which corroborate with apoptotic cell death. Additionally, treatment with the IC50 for 48 hours has promoted cellular and molecular changes that characterize this process, including phosphatidylserine externalization, increase of caspases 3/7, 8 and 9 activity, expression of pro-apoptotic proteins Bax, p21and p27, as well as diminution of Bcl-2 and cyclin-B1. We have also observed increase of cytochrome-c release and NFkB expression. Concerning the security profile, the compound was considered relatively selective, once the IC50 found to basal cell line (185,3 µM) was the double of the obtained to leukemia cell line regarding the same time of exposure (56,76 µM). The outcomes allow us to conclude that LQFM166 was cytotoxic upon leukemia cells K562, promoting morphological and biochemical alterations that indicate apoptotic cell death induction. / Mesmo com os esforços da comunidade científica em descobrir ou desenvolver medicamentos adequados a crescente incidência do câncer e ainda adequados à suas formas multirresistentes, é necessário o desenvolvimento de medicamentos que sejam seletivos e alvo-dirigidos. Assim, no trabalho proposto, foi realizada uma triagem com compostos análogos ao LQFM030, análogo estrutural do Nutlin-1, visando determinar o potencial citotóxico dos mesmos. Além disso, foram investigados a citotoxicidade, as alterações morfológicas e os mecanismos de indução de morte celular do composto escolhido LQFM166 em linhagem de células leucêmicas K562. Paralelamente, foi investigado o perfil de segurança do composto sobre a linhagem basal 3T3, a fim de estimar a DL50 e o Índice de Seletividade do mesmo. Os ensaios de citotoxicidade incluíram o método de redução do sal de tetrazólio (MTT) e o método de incorporação do corante vermelho neutro, para a avaliação do potencial citotóxico sobre as linhagens K562 e 3T3, respectivamente. Para a investigação dos mecanismos de indução de morte celular foi utilizada a técnica de citometria de fluxo, por meio da qual foi realizada a avaliação de parâmetros bioquímicos incluindo progressão ciclo celular, externalização da fosfatidilserina, atividade das caspases 3/7, 8 e 9, liberação do citocromo c, expressão das proteínas p21, p27, Bax, Bcl-2, ciclina-B1 e NFkB, empregando-se técnicas de marcação específicas para cada ensaio. Os dados foram analisados pelo teste t e a diferença entre as médias dos grupos controle e tratado foram consideradas estatisticamente significativas quando p<0,05. Em relação à linhagem leucêmica K562, o composto LQFM166 foi citotóxico apresentando um perfil dose e tempo dependentes. Foram observadas alterações morfológicas a níveis celular e nuclear, após o tratamento com composto, condizentes com o processo de morte celular por apoptose. Adicionalmente, externalização da fosfatidilserina, aumento da atividade das caspases 3/7, 8 e 9, aumento da expressão das proteínas pró-apoptóticas Bax, p21 e p27, bem como diminuição da expressão das proteínas Bcl-2 e ciclina-B1, após tratamento com a CI50 por 48 horas, desencadeou alterações celulares e moleculares que reforçam a sugestão de processo de morte celular por apoptose. Observouse ainda aumento da liberação do citocromo-c e da expressão da proteína NFkB. Já em relação ao perfil de segurança, o composto mostrou-se relativamente seletivo e com menor toxicidade, uma vez que a CI50 encontrada para a linhagem basal (185,3 μM) foi cerca de duas vezes maior ao encontrado para a linhagem tumoral para o mesmo tempo de exposição (56,76 μM). Considerando os resultados obtidos, pode-se concluir que o composto LQFM166 foi citotóxico sobre a linhagem leucêmica K562, desencadeando alterações morfológicas e bioquímicas características de morte celular por apoptose.

Bethoxazin is a broad spectrum industrial biocide with commercial applications as a material preservative; however its mechanism of action has not been investigated. In this study, the chemical reactivity of bethoxazin towards biologically important nucleophiles was assessed with UV-Vis spectroscopy. Bethoxazin reacted with molecules containing free sulfhydryl groups such as glutathione and human serum albumin but not with amino, acetate or phenol containing compounds. Bethoxazin was shown to potently inhibit the growth of the K562 human cancer cell line with an IC50 value in the micromolar range. The sulfydryl fluorescent label ThioGlo-1 was used to investigate the biological effects of bethoxazin in K562 cells and explore its mechanism of action. Bethoxazin inhibited the formation of covalent adducts in K562 cells between the free sulfhydryl group of biomolecules and ThioGlo-1, implying that bethoxazin reacts with molecules containing free sulfhydryl groups. Likewise, when glutathione was depleted in K562 cells, by buthionine sulfoximine, high concentrations of bethoxazin were able to inhibit the formation of covalent adducts between sulfhydryl biomolecules and ThioGlo-1. The growth inhibition assay (MTS) was used to investigate the effect of continuous bethoxazin treatment versus wash out in K562 cells. The MTS assay revealed a reduction in the potency of bethoxazin due to the wash out effect, suggesting that the growth inhibition effects of bethoxazin are likely not due to glutathione depletion. A two-colour flow cytometry analysis of bethoxazin treated K562 cells for eight hours demonstrated that bethoxazin provokes necrosis induced cell death in K562 cells. Taken together, these experimental results demonstrate that the reaction of bethoxazin with proteins containing an accessible sulfhydryl group is more likely to be the mechanism of action of the cell growth inhibition effects rather than glutathione depletion.

Invasion and metastasis of cancer is the leading cause of increased mortality. In addition, haematological malignancies (leukaemia and lymphoma) are a significant cause of morbidity and mortality in both children and adults. Therefore, new treatments which will inhibit cancer progression are required. Integrin adhesion receptors, particularly the RGD-binding integrin subfamily comprising αvβ3, αvβ5, αvβ6, αvβ8, αllbβ3, α5β1, α8β1 and αvβ1 are related to progress and spread of cancer and poor prognosis. Because of the importance of integrin biology in the regulation of cancer dissemination, the integrin receptors are being utilised as targets to regulate cancer progression. The goal of this study was to develop a dual αvβ3/ αIIbβ3 expressing model for testing integrin antagonists. Expression of αv, αIIb, and β3 integrin subunits was characterised using immunofluorescence and flow cytometry in a panel of cell lines. After characterising the expression of αv, αIIb and β3 integrin subunits in inducible and natural expression models (K562 and MCF-7 cells respectively), functional tests for cellular adhesion, detachment and migration were determined. Phorbol 12-myristate 13-acetate (PMA)-treated K562 cells showed increased adhesion on fibrinogen compared to untreated cells. Adhesion of cancer cells (K562 ± PMA and MCF-7) to fibrinogen was inhibited and detachment was induced by the known β3 antagonists, cRGDfV and GR104453. Migration of cancer cells (K562 without PMA and MCF-7) was inhibited by combination of the known β3 antagonists. A panel of 12 novel small molecules developed in the ICT was investigated for cytotoxicity and activity in the validated function assays. ICT9055 was the most potent antagonist in inhibition of cell adhesion, migration, and inducing cell detachment. The data presented in this thesis had selected models and assays for evaluating small molecule integrin antagonists and identified ICT9055 as a promising molecule to develop for further preclinical evaluation. / The Libyan Embassy; Omer Al Mukhtar University, Faculty of Medical Technology, Derna, Libya.

No description available.

Knowledge of plant roots is important for determining plant-soil relationships, managing soil effectively, studying nutrient and water extraction, and creating a soil quality index. Plant root research is limited by the large amount of time and labor required to wash the roots from the soil and measure the viable roots. A root measurement method based on image analysis was proposed to reduce the time and labor requirement. A thinning algorithm-based image analysis method was used to measure corn root length at the planar faces cut from a core sample. The roots were exposed by careful handling and contrasted from the soil by causing autofluorescence using long-wave ultraviolet light. The contrast-enhanced images were stored on the camcorder video tape and digitized by frame grabber. A binary root image was acquired from the digitized gray scale image by a thresholding operation. The binary root image was thinned until the roots were reduced to their basic structure. Root length was calculated from the number of pixels of the root's basic structure. This root length was divided by the removed soil volume of the profile of the core sample to estimate the root length density (RLD, cm root cm⁻³ soil). This estimated RLD was regressed on RLD, measured from washed roots in the same soil core sample, and a linear relationship (R² = 0.96) was obtained. This study indicated that the image analysis root measurement method can determine the length of corn root systems up to 2.5 times faster than by using the conventional method which incorporates a root washing procedure. / Ph. D.

Este trabalho trata do estudo de complexos de rutênio contendo antiinflamatórios não-esteróides, com o objetivo de contribuir para ampliar as pesquisas na área de potenciais metalofármacos antitumorais. A partir de reações do precursor dimetálico [Ru2(O2CCH3)4Cl] com os fármacos carboxílicos sulindaco (HSulin) e diclofenaco de sódio (NaDiclofen) foram isolados, respectivamente, os correspondentes complexos [Ru2(Sulin)4Cl] e [Ru2(Diclofen)4Cl]. A reação entre o monômero [RuCl2(dmso)4] e o meloxicam (H2Melox) deu origem ao derivado misto [Ru(dmso)2(HMelox)2]. Os compostos foram caracterizados por meio de análise elementar, medidas de condutância molar, medidas de susceptibilidade magnética, espectroscopia de absorção eletrônica UV-VIS-IR, espectroscopia vibracional FTIR e Raman, e estudos de análise térmica (TG/DSC/MS). As interações da albumina de soro humana HSA, importante proteína do plasma, com os complexos obtidos, com o análogo [Ru2(IBP)4Cl] (HIBP = ibuprofeno) e também com os fármacos orgânicos não-complexados foram investigadas empregando-se dicroísmo circular, SDS-Page e fluorescência. A atividade antitumoral dos metalofármacos foi avaliada, através de ensaios com MTT, com base nos seus efeitos citotóxicos para a linhagem celular de leucemia humana K562. / This work describes the study of ruthenium complexes containing non-steroidal antiinflammatory drugs with the aim of helping to expand the research in the field of potential anticancer metallodrugs. Reactions of the [Ru2(O2CCH3)4Cl] dimetal complex with sulindac (HSulin) and sodium diclofenac (NaDiclofen) carboxylic drugs gave the correspondent complexes [Ru2(Sulin)4Cl] and [Ru2(Diclofen)4Cl], respectively. The reaction between the [RuCl2(dmso)4] monomer and the meloxicam drug (H2Melox) led to the mixed derivative [Ru(dmso)2(HMelox)2]. The compounds were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility, UV-VIS-IR electronic absorption spectroscopy, Raman and FTIR vibrational spectroscopies and by studies of thermal analysis (TG / DSC / MS). The interactions of human serum albumin (HSA), the major plasma protein, with the obtained complexes, the analogous [Ru2(IBP)4Cl] (= HIBP ibuprofen) and also with the noncoordinated organic drugs have been investigated by circular dichroism, SDS-Page and fluorescence. The antitumor activity of the metallodrugs has been evaluated by MTT assays, on the basis of their cytotoxic effects on K562 human leukemia cell line.

Este trabalho trata do estudo de complexos de rutênio contendo antiinflamatórios não-esteróides, com o objetivo de contribuir para ampliar as pesquisas na área de potenciais metalofármacos antitumorais. A partir de reações do precursor dimetálico [Ru2(O2CCH3)4Cl] com os fármacos carboxílicos sulindaco (HSulin) e diclofenaco de sódio (NaDiclofen) foram isolados, respectivamente, os correspondentes complexos [Ru2(Sulin)4Cl] e [Ru2(Diclofen)4Cl]. A reação entre o monômero [RuCl2(dmso)4] e o meloxicam (H2Melox) deu origem ao derivado misto [Ru(dmso)2(HMelox)2]. Os compostos foram caracterizados por meio de análise elementar, medidas de condutância molar, medidas de susceptibilidade magnética, espectroscopia de absorção eletrônica UV-VIS-IR, espectroscopia vibracional FTIR e Raman, e estudos de análise térmica (TG/DSC/MS). As interações da albumina de soro humana HSA, importante proteína do plasma, com os complexos obtidos, com o análogo [Ru2(IBP)4Cl] (HIBP = ibuprofeno) e também com os fármacos orgânicos não-complexados foram investigadas empregando-se dicroísmo circular, SDS-Page e fluorescência. A atividade antitumoral dos metalofármacos foi avaliada, através de ensaios com MTT, com base nos seus efeitos citotóxicos para a linhagem celular de leucemia humana K562. / This work describes the study of ruthenium complexes containing non-steroidal antiinflammatory drugs with the aim of helping to expand the research in the field of potential anticancer metallodrugs. Reactions of the [Ru2(O2CCH3)4Cl] dimetal complex with sulindac (HSulin) and sodium diclofenac (NaDiclofen) carboxylic drugs gave the correspondent complexes [Ru2(Sulin)4Cl] and [Ru2(Diclofen)4Cl], respectively. The reaction between the [RuCl2(dmso)4] monomer and the meloxicam drug (H2Melox) led to the mixed derivative [Ru(dmso)2(HMelox)2]. The compounds were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility, UV-VIS-IR electronic absorption spectroscopy, Raman and FTIR vibrational spectroscopies and by studies of thermal analysis (TG / DSC / MS). The interactions of human serum albumin (HSA), the major plasma protein, with the obtained complexes, the analogous [Ru2(IBP)4Cl] (= HIBP ibuprofen) and also with the noncoordinated organic drugs have been investigated by circular dichroism, SDS-Page and fluorescence. The antitumor activity of the metallodrugs has been evaluated by MTT assays, on the basis of their cytotoxic effects on K562 human leukemia cell line.