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Abstract(s)
As cianinas, sintetizadas pela primeira vez em 1856 por Greville Williams, são uma classe de compostos catiónicos pertencentes à família dos corantes polimetínicos. A sua estrutura consiste em duas subunidades heterocíclicas azotadas, ligadas por uma cadeia mono- ou polimetínica. Embora estes compostos tenham começado a ser utilizados no mundo da fotografia, nos últimos anos têm sido estudados na deteção e sequenciação de ADN, em citometria de fluxo e em microscopia de fluorescência. As cianinas têm também sido estudadas na doença de Alzheimer; na terapia fotodinâmica como fotossensibilizadores, ou ainda como possíveis agentes anticancerígenos para o cancro do cólon, leucemia e melanoma.
O cancro da mama é uma das neoplasias mundialmente mais comuns no sexo feminino, apresentando-se como a segunda principal causa de morte na mulher. Existem diversos fenótipos e perfis morfológicos associados a esta neoplasia. No entanto, o cancro hormono-dependente representa cerca de 85% de todos os cancros da mama. Atualmente, a terapia hormonal utilizada baseia-se principalmente na utilização de anti-estrogénios ou inibidores da aromatase. No entanto, os diversos efeitos secundários associados a estas terapias, bem como a sua baixa seletividade para as células do cancro da mama e o desenvolvimento de resistência, levam à investigação de novos compostos com possível ação anticancerígena, eficientes no combate a esta doença.
Este trabalho tem como objetivos principais a síntese de novas carbocianinas, variando a sua base heterocíclica, o tamanho da cadeia alquílica e a introdução de alguns grupos substituintes na posição 6; o estudo do efeito destes compostos na proliferação e viabilidade celular em células epiteliais com carcinoma da mama (MCF-7) e em fibroblastos da derme humana, recorrendo ao ensaio de MTT e ao ensaio do ácido bicinconínico (BCA); e ainda o estudo da localização intracelular das carbocianinas através da microscopia confocal de varredura a laser.
Os resultados obtidos no estudo relativo à proliferação e viabilidade dos compostos sintetizados, sugerem que alguns dos compostos estudados estão associados a um processo de apoptose e que o tamanho da cadeia N-alquílica se apresenta como um fator importante na toxicidade destes compostos. No entanto, a importância da restante estrutura não pode ser desprezada.
Cyanines, first synthesized in 1856 by Greville Williams, are a class of cationic compounds that belong to the polymethine dye family. They consist in two nitrogen heterocyclic subunits connected by one mono- or polymethine bond. Although these compounds were first used in the field of photography, in the last years cyanines have been studied in DNA detection and sequencing, in flow cytometry and in fluorescence microscopy. Cyanines have also been widely used in Alzheimer’s disease; as photosensibilizers in photodynamic therapy, or in colon cancer, in leukaemia and melanoma as anticarcinogens. Breast cancer is one of the world’s most common cancer in women, presenting itself as the second leading cause of death in women. There are several phenotypes and morphological profiles associated with the type of cancer. However, the hormone dependent cancer is about 85% of all breast cancer cases. Nowadays, the hormone therapy used is mainly based on the use of anti-estrogens and aromatase inhibitors. Nevertheless, the several secondary effects associated to this therapies, as well as its low selectivity for the breast cancer cells and the development of resistance, lead to the new compounds’ research with potential anti-cancer properties, effective to fight against this disease. The mainly aims of this work are the synthesis of new carbocyanines, varying the heterocyclic base, alkyl chain’s size, and the introduction of some substituent groups in 6 position; the study of their effect on cell proliferation and viability in epithelial breast carcinoma cells (MCF-7) and normal human dermal fibroblasts (NHDF), using the MTT assay and the bicinchoninic acid assay (BCA); and also the study of the carbocyanines’ intracellular localization by confocal laser scanning microscopy. The results obtained in the cell proliferation and viability studies, suggest that some of the used compounds are associated with apoptosis and that the size of the N-alkyl chain presents itself as an important factor in the toxicity of these compounds. However, the importance of the remaining structure can’t be underestimated.
Cyanines, first synthesized in 1856 by Greville Williams, are a class of cationic compounds that belong to the polymethine dye family. They consist in two nitrogen heterocyclic subunits connected by one mono- or polymethine bond. Although these compounds were first used in the field of photography, in the last years cyanines have been studied in DNA detection and sequencing, in flow cytometry and in fluorescence microscopy. Cyanines have also been widely used in Alzheimer’s disease; as photosensibilizers in photodynamic therapy, or in colon cancer, in leukaemia and melanoma as anticarcinogens. Breast cancer is one of the world’s most common cancer in women, presenting itself as the second leading cause of death in women. There are several phenotypes and morphological profiles associated with the type of cancer. However, the hormone dependent cancer is about 85% of all breast cancer cases. Nowadays, the hormone therapy used is mainly based on the use of anti-estrogens and aromatase inhibitors. Nevertheless, the several secondary effects associated to this therapies, as well as its low selectivity for the breast cancer cells and the development of resistance, lead to the new compounds’ research with potential anti-cancer properties, effective to fight against this disease. The mainly aims of this work are the synthesis of new carbocyanines, varying the heterocyclic base, alkyl chain’s size, and the introduction of some substituent groups in 6 position; the study of their effect on cell proliferation and viability in epithelial breast carcinoma cells (MCF-7) and normal human dermal fibroblasts (NHDF), using the MTT assay and the bicinchoninic acid assay (BCA); and also the study of the carbocyanines’ intracellular localization by confocal laser scanning microscopy. The results obtained in the cell proliferation and viability studies, suggest that some of the used compounds are associated with apoptosis and that the size of the N-alkyl chain presents itself as an important factor in the toxicity of these compounds. However, the importance of the remaining structure can’t be underestimated.
Description
Keywords
Cancro da Mama Carbocianinas Citotoxicidade Mcf-7