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Authors
Abstract(s)
Atualmente, o cancro é uma das doenças com maior incidência a nível mundial. O
crescimento populacional, assim como o elevado envelhecimento, associados a fatores
ambientais de risco e a fatores genéticos, têm contribuído para o agravamento das taxas de
morbilidade e mortalidade. Todavia, nos dias de hoje, existem variados tratamentos
associados a esta doença, encontrando-se entre os mais importantes, a quimioterapia, a
radioterapia e a terapia fotodinâmica. A aplicação adequada destas terapias, em conjunto
com um diagnóstico atempado e eficiente, aumentam significativamente as probabilidades
de cura dos pacientes. Dentro da terapia fotodinâmica, as cianinas têm sido amplamente
testadas nos últimos anos. Estas são corantes constituídos por dois anéis heterocíclicos
unidos por uma cadeia metínica com um número ímpar de carbonos. Ao longo dos anos
estes compostos têm sido aplicados em áreas distintas da ciência, sendo utilizados como
agentes fotossensíveis e agentes antiproliferativos. Este trabalho de dissertação tem como
objetivos principais a síntese e a caracterização espectroscópica de novas
monometinocianinas com potencial anticancerígeno e a correspondente avaliação biológica
in vitro, nomeadamente, do seu potencial antiproliferativo em diversas linhas celulares,
assim como estudos adicionais de microscopia de fluorescência e, ainda, estudos
computacionais complementares. Na síntese de monometinocianinas realizada neste
trabalho obtiveram-se rendimentos moderados a bons, sendo que os melhores resultados
foram obtidos na síntese das monometinocianinas assimétricas (72% e 68%). No screening
inicial realizado a uma concentração de 10 µM selecionaram-se as cianinas que
apresentaram um maior potencial antiproliferativo e que demonstraram ter seletividade
para as células cancerígenas. Após essa seleção, procedeu-se à realização do cálculo da
metade da concentração inibitória máxima (IC50). Dos sete compostos testados, destaca-se
uma das monometinocianinas com elevado potencial anticancerígeno, especialmente na
linha celular Caco-2 (IC50= 0,01 µM) e seletividade para esta linha celular cancerígena. No
entanto, serão necessários mais estudos biológicos neste contexto, de forma a elucidar o seu
mecanismo de ação e a respetiva localização celular.
Currently, cancer is one of the diseases with the highest incidence worldwide. Population growth, as well as high growth, associated with environmental risk factors and genetic factors, have contributed to the worsening of morbidity and mortality rates. However, nowadays, there are several treatments associated with this disease, being among the most important, chemotherapy, radiotherapy and photodynamic therapy. The application of these therapies, along with a timely and efficient diagnosis, increases the patient’s chances of cure. Within photodynamic therapy, cyanine dyes have been extensively tested over the years. These are dyes composed of two heterocyclic rings joined by a metal chain with an odd number of carbons. Over the years these compounds have been processed in different areas in different fields of science, being used as photosensitive agents and antiproliferative agents. This dissertation work has as main objectives the synthesis and spectroscopic characterization of new monomethine cyanine dyes with anticancer potential and a corresponding in vitro biological evaluation, namely, their antiproliferative potential in several cell lines, as well as complementary studies of fluorescence microscopy and, further, complementary computational studies, whenever possible. In the synthesis of monomethine cyanine dyes performed in this work, obtained results varied from improved to good, and the best results were obtained in the synthesis of asymmetric monomethine cyanine dyes (72% and 68%). In the initial screening performed at a concentration of 10 µM, cyanine dyes that dissipate a greater antiproliferative potential and that were shown to have selectivity for cancer cells, were selected. After this selection, calculations of half of the maximum inhibitory concentration (IC50) were performed. Of the seven compounds tested, one of the monomethine cyanine dyes stands out, with high anticancer potential especially in the Caco-2 cell line (IC50 = 0.01 µM) and selectivity for this cancer cell line (280). However, more biological studies in this context will be required, in order to elucidate its mechanism of action and its cell location.
Currently, cancer is one of the diseases with the highest incidence worldwide. Population growth, as well as high growth, associated with environmental risk factors and genetic factors, have contributed to the worsening of morbidity and mortality rates. However, nowadays, there are several treatments associated with this disease, being among the most important, chemotherapy, radiotherapy and photodynamic therapy. The application of these therapies, along with a timely and efficient diagnosis, increases the patient’s chances of cure. Within photodynamic therapy, cyanine dyes have been extensively tested over the years. These are dyes composed of two heterocyclic rings joined by a metal chain with an odd number of carbons. Over the years these compounds have been processed in different areas in different fields of science, being used as photosensitive agents and antiproliferative agents. This dissertation work has as main objectives the synthesis and spectroscopic characterization of new monomethine cyanine dyes with anticancer potential and a corresponding in vitro biological evaluation, namely, their antiproliferative potential in several cell lines, as well as complementary studies of fluorescence microscopy and, further, complementary computational studies, whenever possible. In the synthesis of monomethine cyanine dyes performed in this work, obtained results varied from improved to good, and the best results were obtained in the synthesis of asymmetric monomethine cyanine dyes (72% and 68%). In the initial screening performed at a concentration of 10 µM, cyanine dyes that dissipate a greater antiproliferative potential and that were shown to have selectivity for cancer cells, were selected. After this selection, calculations of half of the maximum inhibitory concentration (IC50) were performed. Of the seven compounds tested, one of the monomethine cyanine dyes stands out, with high anticancer potential especially in the Caco-2 cell line (IC50 = 0.01 µM) and selectivity for this cancer cell line (280). However, more biological studies in this context will be required, in order to elucidate its mechanism of action and its cell location.
Description
Keywords
Agentes Antiproliferativos Cancro Cianinas Fluorescência