Corantes esquarílicos com potencial utilização em terapia fotodinâmica do cancro
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2016-06-29
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O principal objectivo deste trabalho foi a síntese e caracterização estrutural de corantes cianínicos esquarílicos e a avaliação da sua citotoxicidade in vitro, no escuro e sob irradiação a um comprimento de onda adequado nas linhas celulares HepG2 e Caco-2, com a finalidade de estudar o seu potencial como agentes fotossensibilizadores para a Terapia Fotodinâmica (PDT) do cancro.
Esta dissertação divide-se em três partes. Na primeira parte é apresentada uma revisão bibliográfica sobre os corantes esquarílicos: estrutura, métodos de síntese, aplicação em PDT e a sua acção biológica.
Seguidamente são apresentados e discutidos os resultados experimentais obtidos sobre a síntese e caracterização estrutural de corantes cianínicos esquarílicos simétricos e de novos corantes cianínicos esquarílicos assimétricos (Figura 1). Os novos compostos foram caracterizados pelas técnicas: ponto de fusão, infravermelho, Ultravioleta-Visivel, Ressonãncia magnética nuclear de protão e de carbono (1H-RMNe 13C-RMN), “Distortionless Enhancement by Polarization” (DEPT) e Espectrometria de massa por electrospray (EMAR-ESI-TOF). Também para estes compostos, são apresentados os valores de rendimento quântico de oxigénio singuleto, tendo-se verificado que a introdução de átomos pesados, tal como o átomo de iodo, aumenta esse valor. Ainda nesta segunda parte, são apresentados e discutidos os resultados da avaliação da sua citotoxicidade após irradiação nas células incubadas com os corantes, sob as condições: não irradiada, irradiada 7 minutos e irradiada 14 minutos com LED’s centrados a 660 nm. Deste estudo salientam-se os resultados obtidos para os compostos zwiteriónicos (S2 = O-) e para o composto aminoesquarílico que possui o grupo NH2 (X=Se, Y=S, S1=I, S2=NH2) que, pode ser considerados como potenciais fotossensibilizadores para PDT do cancro.
Na terceira parte desta dissertação são apresentados os métodos experimentais da síntese dos compostos obtidos bem como a sua caraterização espetroscópica detalhada. São ainda apresentadas detalhadamente as técnicas usadas no estudo do efeito dos compostos sintetizados nas linhas celulares HepG2 e Caco-2.
Tendo em conta os resultados gerais do trabalho, os compostos 4, 19, 21 e 27 apresentam potencial para serem utilizados como eficientes fotossensibilizadores do cancro no futuro, sendo a ordem de potência 19> 4> 27> 21.
The main purpose of this work was the synthesis and structural characterization of squarylium cyanine dyes and evaluation of their in vitro cytotoxicity in the dark and under irradiation at a suitable wavelength in HepG2 and Caco-2cell lines, with the purpose of studying its potential as photosensitizer’s agents for photodynamic therapy (PDT) of cancer. This dissertation is divided into three parts. The first part presents a literature review on the squarylium dyes structure, synthesis methods, application in PDT and its biological action. Below are presented and discussed the experimental results obtained in the synthesis and structural characterization of symmetric squarylium cyanine dyes and new asymmetric squarylium cyanine dyes (Figure 1). The new compounds were characterized by the melting point, Infra-Red, ultraviolet-Visible (UV/Vis), proton and carbon nuclear magnetic resonance (1H-NMR,13C-NMR), Distortionless enhancement by polarization (DEPT) and Electrospray TOF mass spectrometer (HRMS-ESI-TOF) techniques. Also for these compounds are shown the values of quantum yield of singlet oxygen, and it was found that the introduction of heavy atoms such as iodine increases this value. In this second part, are also presented and discussed the results of the evaluation of their cytotoxicity, after irradiation in cells incubated with the dyes under the conditions: non-irradiated, irradiated 7 minutes and irradiated 14 minutes, with LEDs centered at 660 nm. In this study were emphasize the results obtained for the zwitterionic compounds (S2= O-) and for the aminosquarylium dye that have the NH2 group (X = Se, Y = S, S1 = I; S2 = NH2) whichcan be considered as potential photosensitizers for PDT of cancer. The third part of this dissertation presents the experimental methods of synthesis of compounds obtained as well as its detailed spectroscopic characterization. They are also presented in detail the techniques used to study the effect of the compounds synthesized, in the HepG2 and Caco-2cell lines. Given the overall results of the study, the compounds 4, 19, 21:27 have potential to be used as efficient photosensitizers of cancer in the future, with an order of potency 4> 19> 27> 21.
The main purpose of this work was the synthesis and structural characterization of squarylium cyanine dyes and evaluation of their in vitro cytotoxicity in the dark and under irradiation at a suitable wavelength in HepG2 and Caco-2cell lines, with the purpose of studying its potential as photosensitizer’s agents for photodynamic therapy (PDT) of cancer. This dissertation is divided into three parts. The first part presents a literature review on the squarylium dyes structure, synthesis methods, application in PDT and its biological action. Below are presented and discussed the experimental results obtained in the synthesis and structural characterization of symmetric squarylium cyanine dyes and new asymmetric squarylium cyanine dyes (Figure 1). The new compounds were characterized by the melting point, Infra-Red, ultraviolet-Visible (UV/Vis), proton and carbon nuclear magnetic resonance (1H-NMR,13C-NMR), Distortionless enhancement by polarization (DEPT) and Electrospray TOF mass spectrometer (HRMS-ESI-TOF) techniques. Also for these compounds are shown the values of quantum yield of singlet oxygen, and it was found that the introduction of heavy atoms such as iodine increases this value. In this second part, are also presented and discussed the results of the evaluation of their cytotoxicity, after irradiation in cells incubated with the dyes under the conditions: non-irradiated, irradiated 7 minutes and irradiated 14 minutes, with LEDs centered at 660 nm. In this study were emphasize the results obtained for the zwitterionic compounds (S2= O-) and for the aminosquarylium dye that have the NH2 group (X = Se, Y = S, S1 = I; S2 = NH2) whichcan be considered as potential photosensitizers for PDT of cancer. The third part of this dissertation presents the experimental methods of synthesis of compounds obtained as well as its detailed spectroscopic characterization. They are also presented in detail the techniques used to study the effect of the compounds synthesized, in the HepG2 and Caco-2cell lines. Given the overall results of the study, the compounds 4, 19, 21:27 have potential to be used as efficient photosensitizers of cancer in the future, with an order of potency 4> 19> 27> 21.
Descrição
Dissertação de Mestrado em Bioquímica
Palavras-chave
Bioquímica , Cianinas , Corantes esquarílicos , Oxigénio singuleto