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Abstract(s)
Na presente dissertação é apresentada informação relativa à experiência adquirida no estágio curricular em farmácia comunitária, assim como ao trabalho de investigação experimental efetuado paralelamente.
O estágio em farmácia comunitária, realizado maioritariamente na farmácia Holon Covilhã, permitiu-me efetuar tarefas e adquirir conhecimentos no âmbito das várias áreas de intervenção farmacêutica: aprovisionamento, atendimento, gestão de documentação, gestão de qualidade e ações perto da comunidade. Permitiu-me não só perceber um pouco melhor qual a extensão do contributo do farmacêutico para a saúde pública, como também adquirir e aprofundar o meu conhecimento das ciências farmacêuticas.
A investigação experimental, levada a cabo no Centro de Investigação em Ciências da Saúde da Universidade da Beira Interior, incidiu sobre o desenvolvimento e a avaliação biológica de derivados da molécula de estrona funcionalizados nos anéis C e D com potencial atividade anti-tumoral. Com este objetivo, foram sintetizadas algumas moléculas e efetuou-se a avaliação da sua atividade anti-proliferativa em várias linhas celulares humanas. Os resultados desta avaliação biológica parecem demonstrar que o derivado com a substituição 9a-hidroxi-11ß-nitrooxi tem elevada ação anti-proliferativa nas várias linhas celulares estudadas. Adicionalmente, a introdução de uma dupla ligação entre os carbonos 9 e 11 levou também a um marcado efeito anti-proliferativo, principalmente em células HepaRG. Esta modificação estrutural, bem como a introdução de uma lactona no anel D, têm potencial interesse, uma vez que têm sido associadas a uma redução da estrogenicidade, o que poderá ser benéfico na seletividade da sua ação. São necessários, no entanto, estudos mais aprofundados para confirmação e melhoria dos resultados obtidos.
In the current thesis I present information concerning the experience I’ve obtained during my community pharmacy internship, as well as the experimental investigation work that took place in paralel. The community pharmacy internship, held mainly at Holon Covilhã pharmacy, allowed me to execute tasks and obtain knowledge in the many areas of the pharmaceutical practice: provisioning, dispensing/counselling, documentation management, quality management and actions taken near the community. It allowed me not only to better understand the extension of the pharmacyst’s contribution to the public health, but also to acquire and deepen my knowledge of the pharmaceutical sciences. The experimental investigation, that took place at the Health Sciences Investigation Centre at University of Beira Interior, fell upon the development and biological evaluation of functionalized C and D-ring derivatives of the estrone molecule with potential antitumor activity. With this purpose, several molecules where synthesized and their antiproliferative activity in human cell lines was also assessed. The results of this biological evaluation seem to show that the 11ß-nitroxy-9a-hydroxy derivative gives rise to a hight antiproliferative action in the several cell lines that where included in this study. Moreover, the insertion of a double bond between carbon atoms 9 and 11 also lead to a considerable antiproliferative effect, especially in HepaRG cells. This structural modification, as well as the formation of a D ring lactone, have potential interest, since they both have been associated with the reduction of the molecule’s estrogenicity, which may be beneficial in what concerns action selectivity. However, in order to confirm the veracity and improve these results, it is necessary to further investigate the matters at hand.
In the current thesis I present information concerning the experience I’ve obtained during my community pharmacy internship, as well as the experimental investigation work that took place in paralel. The community pharmacy internship, held mainly at Holon Covilhã pharmacy, allowed me to execute tasks and obtain knowledge in the many areas of the pharmaceutical practice: provisioning, dispensing/counselling, documentation management, quality management and actions taken near the community. It allowed me not only to better understand the extension of the pharmacyst’s contribution to the public health, but also to acquire and deepen my knowledge of the pharmaceutical sciences. The experimental investigation, that took place at the Health Sciences Investigation Centre at University of Beira Interior, fell upon the development and biological evaluation of functionalized C and D-ring derivatives of the estrone molecule with potential antitumor activity. With this purpose, several molecules where synthesized and their antiproliferative activity in human cell lines was also assessed. The results of this biological evaluation seem to show that the 11ß-nitroxy-9a-hydroxy derivative gives rise to a hight antiproliferative action in the several cell lines that where included in this study. Moreover, the insertion of a double bond between carbon atoms 9 and 11 also lead to a considerable antiproliferative effect, especially in HepaRG cells. This structural modification, as well as the formation of a D ring lactone, have potential interest, since they both have been associated with the reduction of the molecule’s estrogenicity, which may be beneficial in what concerns action selectivity. However, in order to confirm the veracity and improve these results, it is necessary to further investigate the matters at hand.
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Keywords
Atividade Anti-Tumoral. Derivados da Estrona Farmácia Comunitária Intervenção Farmacêutica Investigação Experimental