| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 856 KB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
O cancro tem sido uma das principais causas de morte no mundo desde o século passado
e é atualmente um dos principais alvos no que concerne a investigação em muitos
campos relacionados com a ciência, nomeadamente a Química Orgânica. A procura por
novas opções terapêuticas é o principal objetivo da investigação oncológica neste
momento, principalmente devido ao facto de a maioria dos tratamentos disponíveis
terem muitos efeitos secundários, embora se tenham tornado mais bem sucedidos ao
longo dos anos.
Um grupo de moléculas que se tem revelado promissor neste domínio é o das
tiossemicarbazonas, devido à sua importante atividade biológica, que está relacionada
com o facto de terem a capacidade de quelar iões metálicos essenciais. As células
cancerígenas têm uma necessidade particular de ferro, que é um metal essencial para
estas células, para o seu crescimento e proliferação. Os agentes quelantes de ferro, como
as tiossemicarbazonas, conseguem remover o Fe dos sistemas biológicos e são capazes
de inibir a atividade de proteínas que necessitam de Fe e que estão envolvidas nas etapas
críticas da síntese de ADN, induzindo lesões celulares. Este facto tem despertado o
interesse por esta área de investigação, estando continuamente à procura de encontrar
novos agentes quelantes de ferro que representem uma opção viável para o tratamento
do cancro.
As tiossemicarbazonas do grupo DpT, incluindo a di-2-piridilcetona-4,4-dimetil-3-
tiossemicarbazona (Dp44mT) e o seu análogo di-2-piridilcetona-4-ciclohexil-4-metil 3-tiossemicarbazona (DpC), demonstraram ser eficazes e seletivas contra uma grande
variedade de tumores, tanto in vitro como in vivo.
O objetivo deste trabalho foi tentar sintetizar análogos da Dp44mT ou da DpC
utilizando o 2-aminofenol como material de partida. Durante este projeto, concentramos-nos em sintetizar os análogos da forma mais otimizada possível e de modo a sintetizar
novas potenciais moléculas que ultrapassassem alguns dos problemas já levantados
pelas moléculas originais. Sempre com o objetivo de estes análogos serem estudados
futuramente em termos de eficácia e atividade.
Palavras-chave: Cancro; Tratamento; Ferro; Tiossemicarbazonas; Análogos
Cancer has been one of the main causes of death in the world since the past century and it is currently one of the major targets when it comes to research in many fields related with science such as Organic Chemistry. Search for new therapies is the main goal of oncology research at the moment, mostly connected with the fact that most of the treatments available have many side effects, although they have become more successful throughout the years. One group of molecules that has been shown promising in this field are thiosemicarbazones due to their significant biologic activity, this is linked with the fact that they have the ability to chelate essential metal ions. Cancer cells have a particular need of iron which is a key metal for these cells, for their growth and proliferation. Iron chelators like thiosemicarbazones can remove Fe from biological systems and are able to inhibit the activity of Fe-requiring proteins involved in the critical steps of DNA synthesis leading to induced cellular injury. This has dispelled interest in this area of research, that is continuously trying to find more iron chelators that represent a viable option for cancer treatment. Thiosemicarbazone of the DpT group including di-2-pyridylketone-4,4-dimethyl-3- thiosemicarbazone (Dp44mT) and its analogue di-2-pyridylketone-4-cyclohexyl-4- methyl-3- thiosemicarbazone (DpC), have been shown to be effective and selective against a wide variety of tumours both in vitro and in vivo. The aim of this study was to try to synthesise analogues of the di-2-pyridylketone’4,4 dimethyl 3 thiosemicarbazone (Dp44mT) or di-2-pyridylketone-4-cyclohexyl-4- methyl-3-thiosemicarbazone (DpC) using 2-aminophenol as a starting material. During this project we focused on synthesising the analogues in the most optimised way possible and in order to potentially synthesise new molecules that would overcome some problems that the original molecules showed. With the aim of these analogues being studied in the future in terms of efficacy and activity. Keywords: Cancer; Treatment; Iron; Thiosemicarbazones; Analogues;
Cancer has been one of the main causes of death in the world since the past century and it is currently one of the major targets when it comes to research in many fields related with science such as Organic Chemistry. Search for new therapies is the main goal of oncology research at the moment, mostly connected with the fact that most of the treatments available have many side effects, although they have become more successful throughout the years. One group of molecules that has been shown promising in this field are thiosemicarbazones due to their significant biologic activity, this is linked with the fact that they have the ability to chelate essential metal ions. Cancer cells have a particular need of iron which is a key metal for these cells, for their growth and proliferation. Iron chelators like thiosemicarbazones can remove Fe from biological systems and are able to inhibit the activity of Fe-requiring proteins involved in the critical steps of DNA synthesis leading to induced cellular injury. This has dispelled interest in this area of research, that is continuously trying to find more iron chelators that represent a viable option for cancer treatment. Thiosemicarbazone of the DpT group including di-2-pyridylketone-4,4-dimethyl-3- thiosemicarbazone (Dp44mT) and its analogue di-2-pyridylketone-4-cyclohexyl-4- methyl-3- thiosemicarbazone (DpC), have been shown to be effective and selective against a wide variety of tumours both in vitro and in vivo. The aim of this study was to try to synthesise analogues of the di-2-pyridylketone’4,4 dimethyl 3 thiosemicarbazone (Dp44mT) or di-2-pyridylketone-4-cyclohexyl-4- methyl-3-thiosemicarbazone (DpC) using 2-aminophenol as a starting material. During this project we focused on synthesising the analogues in the most optimised way possible and in order to potentially synthesise new molecules that would overcome some problems that the original molecules showed. With the aim of these analogues being studied in the future in terms of efficacy and activity. Keywords: Cancer; Treatment; Iron; Thiosemicarbazones; Analogues;
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Cancer Treatment Iron Thiosemicarbazones Analogues Mestrado Integrado - 2023