Title from PDF of title page (University of Missouri--Columbia, viewed on March 2, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dr. Kent S. Gates, Dissertation Supervisor. Vita. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Apr 14

Thesis (M.S.)--University of North Carolina at Wilmington, 2006. / Includes bibliographical references (leaves: 49-50)

Discovery of cheap, nontoxic and readily available antiatherosclerotic drugs is an extraordinary challenge in this modern world. Atherosclerosis and cardiovascular diseases have been predicted to be the leading cause of death by the year 2030. Hence, this thesis was designed to search for plant (s) with anti-atherogenic properties, investigate its possible side effects and extrapolate its likely mechanism(s) of action. An ethnobotanical survey was employed in identification of locally important plants used for the management and treatment of cardiovascular diseases and its predisposing factors in Nkonkobe Municipality, Eastern Cape in South Africa. Information on the names of plants, their parts used and methods of preparation was collected through a questionnaire which was administered to herbalists, traditional healers and rural dwellers. The most frequently used plant (Rhizomes of Tulbaghia violacea Harv.) was investigated for toxicity using brine shrimp lethality (in vitro) and in vivo toxicity test (acute and subchronic) on rats to determine safety dosage. The in vitro antioxidant and free radical scavenging activity of the plant was investigated using models such as 1,1-diphenyl-2- picrylhydrazyl (DPPH), superoxide anions, hydrogen peroxide (H2O2), nitric oxide (NO), 2,2’- azinobis [3-ethylbenzothiazoline-6-sulfonic acid] diammonium salt (ABTS), lipid peroxidation inhibition and the ferric reducing agent. Phytochemical content and the effect of oral administration of fresh methanolic extract rhizomes of Tulbaghia violacea (250, 500 mg/kg. bwt/day) on Lipid peroxidation (TBARS), serum and tissue antioxidant enzymes in normal, hypercholesterolemic and diet induced atherogenic rats were also assessed. More so, the potential of the extract (250 and 500 mg/kg. bwt) to protect against atherogenic diet (4 percentage cholesterol 1 pecentage cholic acid and 0.5 percentage thiouracil) induced fatty streaks formation, dyslipidemia, oxidative stress and endothelial dysfunction was also investigated. Ethnobotanical study revealed that 19 plant species are used for the treatment of heart related diseases in the Municipality. 53 percentage of the plants mentioned were used for the management of chest pain, 47 percentage for high blood pressure, 42 percent for heart disease, 16 percentage for stroke and 11 percentage for the treatment of hypercholesterolemia. Tulbaghia violacea was repeatedly mentioned as the plant species used for the treatment of high blood pressure and predisposing factors in the study area. The brine shrimp cytotoxicity test revealed that fresh, dried methanolic extracts and essential oil of the T. violacea exhibited a high degree of cytotoxic activity with IC50 values of 18.18 (fresh) and 19.24 (dried) μg/ml. An IC50 value of 12. 59 μg/ml was obtained for the essential oil of the plant. The low cytotoxicity values obtained, suggested that rhizome of T. violacea may serve as a potential source of antimicrobial and anticancer agents. In vivo acute study of single oral administration of 5g/kg dose does not produce mortality or significant behavioral changes during 14 days observation. In the sub-chronic study, the extract (250, 500 mg/kg/bwt/ day) administered for a period of 28 days showed no mortality or morbidity. The weekly body and organ weight of the rats showed no significant differences between the control and the rats treated with the extract. The extract at all doses does not show any effect on of biomarkers of liver or renal damage. However, a significant decrease in the activity of ƔGT was observed in the extract treated groups. Hematological evaluation revealed that oral administration of fresh methanolic extracts of rhizomes of T. violacea does not cause anaemia or leucocytosis in the animals. Furthermore, histopathology results of the internal organs revealed no detectable inflammation. These results demonstrated that the rhizome extract of T. violacea was potentially safe for consumption orally even in chronic concentration. In vitro antioxidant evaluation showed that the essential oil, fresh and dried methanolic extracts exhibited potent antioxidant activities in a concentration dependent manner. Phytochemical investigation reveals that the fresh and the dry extract of RTV are rich in flavonoid, flavonol, phenols, tannin and proanthocyanidin, while the essential oil contained dimethy disulfide, dimethyl trisulfide, (methyl methylthio) methyl, 2,4-dithiapentane (11.35 percent) and (methylthio) acetic acid, 2- (methylthio) ethanol, 3-(methylthio) - and propanenitrile (7.20 percent). The fresh extract had higher radicals scavenging activity than the essential oil or dried extract, with 50 percentage inhibition of DPPH, hydrogen peroxide and lipid peroxidation at a concentration of 35.0 ± 0.12, 19.3 ± 0.11 and 17.9 ± 0.15 μg/ml respectively. Oral administration of methanolic extract of RTV in 125, 250 and 500 mg/kg to female Wistar rats significantly inhibited reduction of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). The extracts also inhibited (p< 0.05) lipid peroxidation in normal, high cholesterol and diet induced atherosclerosis fed rats in a dose dependant manner. Also the extract (250 and 500 mg/kg/bwt/day) caused a significant (p<0.05) improvement in body weight of treated animals compared with untreated hypercholesterolemia control rats. The extracts also protected significantly (p<0.05) against atherogenic diet induced liver damage or fatty streaks formation in the aorta as revealed by histological examination. The anti-cholesterolemia and anti-atherosclerotic activities of the extract compared favorably well with standard drugs Gemfibrozil and Atorvastatin respectively. Conclusively, rhizomes of T. violacea possess significant anti-atherogenic activity and its mechanism of action(s) may be due to its antioxidant and anti-hypercholesterolemia properties. The results of this study also suggested that rhizome of T. violacea is relatively safe for human consumption and it may be used as an alternative to garlic.

Syntheses of Schiff bases were carried out by reacting salicylaldyhde, ortho-vanillin, para-vanillin or vanillin with aniline, 1-aminonaphthalene, 4- and 3-aminopyridine, and also with 2- and 3-aminomethylpyridine. The various Schiff bases obtained from the condensation reaction were reacted with CoCl₂.6H₂0, triethylamine stripped CoCl₂.6H₂0 or Co(CH₃COO)₂ to form cobalt(Il) complexes of ratio 2:1. The complexes obtained from cobalt chloride designated as the "A series" are of the general formulae ML₂X₂.nH₂0 , (L = Schiff base, X = chlorine) while those obtained from cobalt acetate or triethylamine stripped cobalt chloride denoted as "B" and C" are of the general formulae ML₂. nH₂0. The few complexes that do not follow the general formulae highlighted above are: IA [M(HL)₃.Cl₂], (L = N-phenylsalicylaldimine), 4A = (MLCl₂), (L = N-phenylvanaldiminato), 7 A and 21 A (ML₂), (L = N-naphthyl-o-vanaldiminato, and N-methy-2-pyridylsalicylaldiminato respectively), 8A = MLCI, (L = N-naphthylvanaldiminato), 12A = M₂L₃Cl₂, (L = N-4-pyridylvanaldiminato), 15A (MLCI), (L = N-3-pyridyl-o-vanaldiminato). The ligands and their complexes were characterized using elemental analyses and cobalt analysis using ICP, FT-IR spectroscopy (mid and far-IR), NIR-UV/vis (diffuse reflectance), UV/vis in an aprotic and a protic solvents, while mass spectrometry, ¹HNMR and ¹³CNMR, was used to further characterized the ligands. The tautomeric nature of the Schiff bases were determined by examining the behaviour of Schiff bases and their complexes in a protic (e.g. MeOH) and non-protic (e.g. DMF) polar solvents. The effects of solvents on the electronic behaviour of the compounds were also examined. Using CDCl₃, the NMR technique was further used to confirm the structures of the Schiff bases. The tentative geometry of the complexes was determined using the spectra information obtained from the far infrared and the diffuse reflectance spectroscopy. With few exceptions, most of the "A" series are tetrahedral or distorted tetrahedral, while the "B + C" are octahedral or pseudooctahedral. A small number of complexes are assigned square-planar geometry owing to the characteristic spectral behaviour shown. In order to determine their biological activity, two biological assay methods (antimicrobial testing and brine shrimp lethality assay) were used. Using disc method, the bacteriostatic and fungicidal activities of the various Schiff bases and their respective complexes to Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa as well as Aspergillus niger, were measured and the average inhibition zones are tabulated and analysed. Both the Schiff bases and their complexes showed varying bacteriostatic and fungicidal activity against the bacteria and fungus tested. The inhibition activity is concentration dependent and potential antibiotic and fungicides are identified. To determine the toxicity of the ligands and their corresponding cobalt(II) complexes, brine shrimp lethality assay was used. The LD₅₀ of the tested compounds were calculated and the results obtained were tabulated for comparison.

Made available in DSpace on 2014-08-13T14:50:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-31Bitstream added on 2014-08-13T18:00:22Z : No. of bitstreams: 1 000760138.pdf: 1342792 bytes, checksum: 04e3113cab00466cb2ff5442738feb1d (MD5) / Estudos prévios têm demonstrado que baixas concentrações de agentes antineoplásicos como ciclofosfamida e paclitaxel (PAC) modulam positivamente a resposta imune, estimulando linfócitos T e células dendríticas (DCs). Além disso, são capazes de aumentar a imunogenicidade de células de câncer colorretal humano HCT-116, e de induzir a transcrição de genes de proteínas de choque térmico (HSPs). No presente trabalho, tivemos como objetivo avaliar a expressão das HSPs 40, 70 e 90 e comparar o efeito da concentração efetiva mínima (CEM) com a concentração não-tóxica (CNT) de PAC sobre a imunogenicidade das células HCT-116. Células HCT-116 foram tratadas com a CEM ou com a CNT de PAC. Lisados tumorais foram analisados quanto à expressão das HSPs e utilizados para sensibilizar DCs derivadas de monócitos de sangue periférico de indivíduos normais. As DCs foram avaliadas quanto ao seu fenótipo e foram co-cultivadas com linfócitos T alogênicos para a avaliação da capacidade de estimulação desses linfócitos. O tratamento das células tumorais com ambas as concentrações da droga induziu o aumento da expressão de HSP40, enquanto a produção de HSP70 e HSP90 foram aumentadas apenas pela CEM e pela CNT, respectivamente. Observou-se ligeiro, mas não significante aumento da capacidade de indução da resposta alogênica. Houve também uma tendência ao aumento da expressão de CD40 nos grupos HCT, CEM e CNT. É possível que a expressão das HSPs contribua para o aumento de imunogenicidade induzido pelo PAC. A CEM é menos eficiente que a CNT em aumentar a imunogenicidade das células tumorais, mas não prejudica a capacidade das DCs de induzir a resposta alogênica nem seus marcadores fenotípicos de ativação / Colorectal cancer (CRC) is one of the main causes of death worldwide and its conventional treatment is based on surgery, cytotoxic chemotherapy and radiotherapy, or a combination of these therapeutic modalities. The main chemotherapeutic agents for fighting CRC are metrotexate, 5-aza-2-deoxycitidine, taxans and 5-fluorouracil. Usually, their administration is based on maximum tolerable doses, but it has been shown that low concentrations of most of these drugs upregulate the immune system, both enhancing the immune responsiveness and increasing the immunogenicity of tumor cells. These features are associated with translational changes of a couple of genes, among them, there is an increased expression of heat-shock proteins (HSPs). Although the expression of HSPs may represent an adaptive response of tumor cells to the drug-induced damages, there is evidence that some of these proteins are fundamental for antigen processing and presentation by antigen-presenting cells. Then, in the present review we aimed to show that increased expression of HSPs by drug-treated tumor cells may be favorable for the development of an effective immune response, and that this phenomenon should enhance the combinatory schedules of chemotherapy and immunotherapy

A própolis vermelha brasileira tem atraído interesses científicos e econômicos devido às suas variadas atividades biológicas. Este produto natural possui composição química variada de acordo com a região na qual é encontrado, sendo necessária uma completa caracterização química para cada tipo de própolis, a fim de se elucidar os compostos presentes e responsáveis pela atividade biológica observada. Neste trabalho, buscou-se caracterizar quimicamente os extratos da própolis vermelha brasileira, avaliar sua atividade antitumoral, bem como alguns mecanismos de morte celular, além de investigar o padrão proteico de células tumorais de laringe (Hep-2) e não tumorais de rim (Hek-293) tratadas e não tratadas com extratos da própolis vermelha através da análise proteômica comparativa. A caracterização química mostrou que a própolis apresenta moléculas complexas, principalmente isoflavonoides, que possuem importantes atividades biológicas, dentre elas a atividade antitumoral. A atividade citotóxica de duas frações e do extrato hidroalcoólico da própolis foi avaliada na linhagem tumoral Hep-2, a qual se revelou mais citotóxica nos tratamentos com as frações investigadas. Os ensaios de citometria mostraram que as células que receberam tratamento apresentaram menor potencial de membrana mitocondrial, maior quantidade de células em apoptose tardia (TUNEL e Anexina-V/PI), menor geração de espécies reativas do oxigênio e o aumento de fragmentação do DNA. Além disto, as colorações revelaram a presença de corpos apoptóticos e condensação de cromatina. A análise proteômica permitiu a comparação dos mapas proteicos da linhagem Hep-2, na ausência ou presença de extratos da própolis vermelha, com a linhagem não tumoral Hek-293. Estas proteínas foram classificadas de acordo com os processos biológicos as quais estão envolvidas. Além disto, doze proteínas identificadas na linhagem Hep-2 apresentaram expressão reduzida comparada ao grupo controle, dentre as quais muitas estão presentes em grande quantidade em outros tumores e são consideradas biomarcadores tumorais. Os resultados, de forma geral, mostram que a própolis interfere em um conjunto de eventos intracelulares e, assim, passa a ser uma candidata promissora para inibir o crescimento celular e contribuir para os diferentes passos relacionados com o processo de carcinogênese. Embora os mecanismos moleculares pelos quais a própolis vermelha interaja com o metabolismo das células permaneçam ainda desconhecidos, estudos adicionais servirão para melhor elucidar a atividade antitumoral da própolis vermelha brasileira e de suas frações. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2017-04-18T16:59:16Z No. of bitstreams: 1 Tese Caroline Olivieri da Silva Frozza.pdf: 11179534 bytes, checksum: b2ae6a4dfa6013728ea3f7c81bc40380 (MD5) / Made available in DSpace on 2017-04-18T16:59:16Z (GMT). No. of bitstreams: 1 Tese Caroline Olivieri da Silva Frozza.pdf: 11179534 bytes, checksum: b2ae6a4dfa6013728ea3f7c81bc40380 (MD5) Previous issue date: 2017-04-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES. / The Brazilian red propolis has attracted scientific and economic interests due to its varied biological activities. This natural product has diversify chemical composition according to the region in which it is found, then it is necessary a complete chemical characterization for each type of propolis, in order to elucidate the present compounds and responsible for the biological activity observed. In this work, we attempted to chemically characterize the extracts of Brazilian propolis, evaluate their antitumor activity as well as some cell death mechanisms, and to investigate the protein profile of larynx tumor cells treated and not treated with propolis extracts through comparative proteomic analysis. The chemical characterization showed that propolis has complex molecules, particularly isoflavones, which present significant biological activities, such as antitumor activity. The cytotoxic activity of two fractions and of the hydroalcoholic extract of propolis was assessed in Hep-2 tumor cell line, which proved to be more cytotoxic treatments in the investigated fractions. Flow cytometric assays showed that treated cells had lower mitochondrial membrane potential, increased amount of cells in late apoptosis (TUNEL and Annexin-V / PI), less generation of reactive oxygen species and increase in DNA fragmentation. Furthermore, the staining revealed the presence of apoptotic bodies and chromatin condensation. The proteomic analysis has allowed comparison of the maps of the protein Hep-2 cell line, in the absence or presence of propolis extracts, with non-tumor cell line Hek-293. These proteins were classified according to the biological processes which they are related. Besides, twelve identified proteins in Hep-2 showed reduced expression from the control group. Between them, many are presented in large quantities in other tumors and are considered tumor biomarkers. The results in general show that propolis interferes with a series of intracellular events and hence becomes a promising candidate to inhibit cell growth and contribute to the different steps relating to the process of carcinogenesis. Although the molecular mechanisms by which propolis interact with the metabolism of the cells remain unknown, further study will serve to better elucidate the antitumor activity of Brazilian propolis and its fractions.

A própolis vermelha é uma resina natural produzida por abelhas do gênero Apis a partir de exsudados vegetais e tem atraído a atenção dos pesquisadores de todo o mundo devido à sua potente atividade em diversos modelos biológicos. Essa resina natural é rica em polifenóis e compostos voláteis, sendo que mais 300 compostos químicos já foram identificados em amostras de diferentes regiões. Técnicas de identificação química de alta precisão são imprescindíveis para a correta elucidação dos compostos químicos presentes nas amostras e para o entendimento dos efeitos biológicos. Neste estudo, buscou-se utilizar técnicas de fracionamento como uma metodologia capaz de ser explorada em estudos envolvendo amostras de própolis vermelha, buscando-se a identificação e caracterização de frações ativas, bem como o uso de modelos celulares de câncer de cólon para o screening de moléculas bioativas. As frações ativas foram identificadas por meio HPLC-MS e ESI-MS/MS, evidenciando uma composição química complexa baseada em compostos fenólicos e flavonoides. Entre os resultados obtidos, destacam-se as frações 05 e 06, as quais foram capazes de produzir inibição significativa sobre as linhagens tumorais HT-29 e HCT-116, respectivamente, com menores efeitos sobre as células não-tumorais. As frações obtidas no estudo apresentaram menor diversidade química do que a encontrada no extrato total da própolis, favorecendo a sua bioatividade in vitro, e, como resultado, esta técnica pode favorecer a descoberta e o desenvolvimento de novos fármacos utilizando a própolis como fonte de potencial de moléculas contra o câncer. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2017-04-26T12:12:54Z No. of bitstreams: 1 Dissertacao Denis Amlton dos Santos.pdf: 1867020 bytes, checksum: 9a2b6e047762ce4edebdc69379893739 (MD5) / Made available in DSpace on 2017-04-26T12:12:54Z (GMT). No. of bitstreams: 1 Dissertacao Denis Amlton dos Santos.pdf: 1867020 bytes, checksum: 9a2b6e047762ce4edebdc69379893739 (MD5) Previous issue date: 2017-04-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES. / Red propolis is a natural resin produced by bees of the genus Apis from plant exudates and has attracted the attention of researchers worldwide due to its potent activity in several biological models. This natural resin is rich in polyphenols and volatile compounds and more than 300 chemical compounds have been identified in samples from different regions. High precision chemical identification techniques are essential for the correct elucidation of the chemical compounds present in the samples and for the understanding of the biological effects. In this study, we sought to use fractionation techniques as a methodology able to be explored in studies involving samples of red propolis, seeking the identification and characterization of active fractions, as well as the use of cellular models of colon cancer for screening of bioactive molecules. The active fractions were identified by techniques of HPLC-MS and ESI-MS/MS, evidencing a complex chemical composition based on phenolic compounds an flavonoids. Among the obtained results, we highlight the fractions 05 and 06, which are able to produce significant inhibition on the HT-29 and HCT-116 tumor lines.The fractions obtained in this study showed lower chemical diversity than that found in the total extract of propolis, favoring its bioactivity, and as a result, this technique may favor the discovery and development of new drugs using propolis as a potential source of molecules against cancer.

Orientador: Ramon Kaneno / Coorientador: Graziela Gorete Romagnoli / Banca: Maria Teresinha Serrão Peraçoli / Banca: Orlando Garcia Ribeiro Filho / Resumo: Estudos prévios têm demonstrado que baixas concentrações de agentes antineoplásicos como ciclofosfamida e paclitaxel (PAC) modulam positivamente a resposta imune, estimulando linfócitos T e células dendríticas (DCs). Além disso, são capazes de aumentar a imunogenicidade de células de câncer colorretal humano HCT-116, e de induzir a transcrição de genes de proteínas de choque térmico (HSPs). No presente trabalho, tivemos como objetivo avaliar a expressão das HSPs 40, 70 e 90 e comparar o efeito da concentração efetiva mínima (CEM) com a concentração não-tóxica (CNT) de PAC sobre a imunogenicidade das células HCT-116. Células HCT-116 foram tratadas com a CEM ou com a CNT de PAC. Lisados tumorais foram analisados quanto à expressão das HSPs e utilizados para sensibilizar DCs derivadas de monócitos de sangue periférico de indivíduos normais. As DCs foram avaliadas quanto ao seu fenótipo e foram co-cultivadas com linfócitos T alogênicos para a avaliação da capacidade de estimulação desses linfócitos. O tratamento das células tumorais com ambas as concentrações da droga induziu o aumento da expressão de HSP40, enquanto a produção de HSP70 e HSP90 foram aumentadas apenas pela CEM e pela CNT, respectivamente. Observou-se ligeiro, mas não significante aumento da capacidade de indução da resposta alogênica. Houve também uma tendência ao aumento da expressão de CD40 nos grupos HCT, CEM e CNT. É possível que a expressão das HSPs contribua para o aumento de imunogenicidade induzido pelo PAC. A CEM é menos eficiente que a CNT em aumentar a imunogenicidade das células tumorais, mas não prejudica a capacidade das DCs de induzir a resposta alogênica nem seus marcadores fenotípicos de ativação / Abstract: Colorectal cancer (CRC) is one of the main causes of death worldwide and its conventional treatment is based on surgery, cytotoxic chemotherapy and radiotherapy, or a combination of these therapeutic modalities. The main chemotherapeutic agents for fighting CRC are metrotexate, 5-aza-2-deoxycitidine, taxans and 5-fluorouracil. Usually, their administration is based on maximum tolerable doses, but it has been shown that low concentrations of most of these drugs upregulate the immune system, both enhancing the immune responsiveness and increasing the immunogenicity of tumor cells. These features are associated with translational changes of a couple of genes, among them, there is an increased expression of heat-shock proteins (HSPs). Although the expression of HSPs may represent an adaptive response of tumor cells to the drug-induced damages, there is evidence that some of these proteins are fundamental for antigen processing and presentation by antigen-presenting cells. Then, in the present review we aimed to show that increased expression of HSPs by drug-treated tumor cells may be favorable for the development of an effective immune response, and that this phenomenon should enhance the combinatory schedules of chemotherapy and immunotherapy / Mestre

Orientador: Eduardo Maffud Cilli / Banca: Thatyane Morimoto Nobre-Pavinatto / Banca: Karen Cristine Martinez de Moraes / Resumo: A síntese de pept ídeos em fase sólida mostra - se como uma importante ferramenta para a modelagem de macromoléculas biológicas, sendo algumas de interesse quimioterápico. Desde que foi descrita pela primeira vez, est a técnica tem possibilitado a síntese de inúmeros peptídeos e o estudo aprofundado dessas moléculas. Peptídeos líticos apresentam - se como novas moléculas promissoras contra neoplasias, sendo seu mecanis mo de ação ainda ob scuro. O c âncer é uma doença causada por fatores que provocam o desenvolvimento anormal de células do organismo. Estas células tendem a ser agressivas e incontroláveis, determinando a formação de tumores. O câncer cervic al é um dos mais comuns, afetando pr incipalmente regiões pouco desenvolvidas . I nfecções pelo vírus HPV, tabagismo, falta de higiene pessoal e relações sexuais sem o uso de preservativos são as principais causas pelo aparecimento da doença. O HPV é um vírus não envelopado, de dupla fita de DNA circular e que promove infecção em células basais em divisão do epitélio. Este trabalho descreve a síntese, purificação e caracterização d o peptídeo lítico Hecate ( FALALKALKKALKKLKKALKKAL ) e do conjugado ácido gálico - H ecate (AG - FALALK ALKKALKKLKKALKKAL ) . Estas moléculas foram utilizadas na busca de novas terapias contra o câncer cervical causado por infecção viral e n o entendimento d e seu modo de ação. Os resultados mostraram que o peptídeo apresenta alta potencialidade contra o câncer cervical, mas o acoplamento do ácido gálico na sua po sição amino terminal, além de diminuir a potencialidade contra o câncer, aument ou sua atividade hemolítica. Estas diferenças estão diretamente relac ionadas com a diferença de carga dos dois compostos, a diferente composição lipídica das células e a estrutura secundária dos compostos. / Abstract: The solid phase peptide synthesis is shown as an important tool for modeling of biological macromolecules, and some chemotherapeutic interest . Since it was first described this technique has made possible the synthesis of numerous peptides and car eful study of these molecules. L ytic peptides are presented as promising new molecules against cancer, and the action mechanism is still unclear. Cancer is a disease caused by factors that cause abnormal development of the body's cells. These cells tend to be aggressive and uncontrollable, causing tumor formation. Cervical cancer is the most common, affecting mainly underdeveloped regions. Infection by the HPV virus, smoking, lack of personal hygiene and sex without protection are the main causes for the ap pearance of the disease. The HPV virus is a non - enveloped virus with circular double - stranded DNA and promotes infection in the dividing basal cells of the epithelium. This work describes the synthesis, purification and characterization of the lytic peptid e Hecate (FALALKALKKALKKLKKALKKAL) and conjugate gallic acid - Hecate (GA - FALALKALKKALKKLKKALKKAL). These molecules were used in the search for new therapies against cervical cancer caused by viral infection and understanding of their mode of action. The res ults showed that the peptide has a high potential against cervical cancer, but the coupling of gallic acid in i ts amino terminal position reduces the potential of peptide for cancer and increases his hemolytic activity. These differences are directly relat ed to the charge difference of the two compounds, the different lipid composition of cells and the secondary structure of the compounds. / Mestre