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Abstract(s)
A tuberculose continua a ser das doenças que mais afeta o ser humano hoje em dia. Cada vez mais hĂĄ uma procura para alcançar novos fĂĄrmacos e novas terapĂȘuticas para combater esta infeção. Embora nĂŁo continue a ser tĂŁo prevalente como era hĂĄ uns anos atrĂĄs, continuam a surgir milhĂ”es de novos casos todos os anos por todo o mundo.
Um dos problemas que estå mais associado com a tuberculose é o fato do seu agente de infeção o Mycobacterium tuberculosis estar cada vez mais resistente aos fårmacos usados no tratamento desta infeção. Assim, hå uma necessidade em descobrir novos fårmacos capazes de combater estas novas estirpes resistentes.
Um novo alvo terapĂȘutico a explorar sĂŁo as nitroredutases que sĂŁo responsĂĄveis por ativarem os nitroimidazĂłis e assim produzir metabolitos e mecanismos de ação que impeçam esta bactĂ©ria de sobreviver. Nos Ășltimos anos os nitroimidazĂłis tĂȘm sido alvo de grande pesquisa, sendo a pretomanida e a delamanida os Ășltimos a serem aprovados para eliminar a bactĂ©ria da tuberculose multirresitente. Estes dois fĂĄrmacos sĂŁo nitroimidazĂłis bicĂclicos e atravĂ©s de ensaios clĂnicos demonstraram resultados bastante bons e com sucesso. Com base em diversos estudos concluiu-se que nĂŁo sĂŁo tĂłxicos para o ser humano e tĂȘm bons resultados terapĂȘuticos. HĂĄ que explorar nĂŁo sĂł, a sua atividade, mas tambĂ©m a sua interação com os restantes fĂĄrmacos utilizados no tratamento da tuberculose.
Devido ao mecanismo de ação destes fĂĄrmacos, que tem por base uma redução do grupo nitro por uma nitroredutase dependente de deazaflavina, estes novos nitroimidazĂłis, surgem como uma nova alternativa terapĂȘutica nas infeçÔes multirresistentes. Embora tenham algumas diferenças entre si, tĂȘm o mesmo mecanismo desencadeado pela nitroredutase. Estas proteĂnas, sĂŁo um alvo terapĂȘutico a ter em consideração na produção de novos fĂĄrmacos sendo importante a sua contĂnua investigação, de forma a criar segurança e eficĂĄcia nos produtos a serem disponibilizados no mercado.
Tuberculosis continues to be one of the diseases that affects most human beings today. There is an increasing demand for new drugs and new therapies to fight this infection. Although it is not as prevalent as it was a few years ago, there are still millions of new cases every year all over the world. One of the most associated problems with tuberculosis is the fact that its agent of infection, Mycobacterium tuberculosis, is increasingly resistant to the drugs used to treat this infection. Thus, there is a need to find new drugs capable of combating these new resistant strains. A new therapeutic target to explore is nitroreductases, which are responsible for activating nitroimidazoles and thus produce metabolites and mechanisms of action that prevent these bacteria from surviving. In recent years nitroimidazoles have been the subject of a great deal of research, with pretomanid and delamanid being the latest to be approved for eliminating the multiresitant tuberculosis bacteria. These two drugs are bicyclic nitroimidazoles and clinical trials have shown very good and successful results. Based on several studies, they showed no signs of toxicity in humans and demonstrated good therapeutic results. It is necessary to explore not only their activity, but also their interaction with the other drugs used in the treatment of tuberculosis. Due to the mechanism of action of these drugs, which is based on a reduction of the nitro group by a deazaflavin-dependent nitroreductase, these new nitroimidazoles appear as a new therapeutic alternative in multidrug-resistant infections. Although they have some differences between them, they have the same mechanism triggered by a nitroreductase. These proteins are a therapeutic target to be taken into consideration in the production of new drugs, and its continuous research is important, to create safety and efficacy in products to be made available in the market.
Tuberculosis continues to be one of the diseases that affects most human beings today. There is an increasing demand for new drugs and new therapies to fight this infection. Although it is not as prevalent as it was a few years ago, there are still millions of new cases every year all over the world. One of the most associated problems with tuberculosis is the fact that its agent of infection, Mycobacterium tuberculosis, is increasingly resistant to the drugs used to treat this infection. Thus, there is a need to find new drugs capable of combating these new resistant strains. A new therapeutic target to explore is nitroreductases, which are responsible for activating nitroimidazoles and thus produce metabolites and mechanisms of action that prevent these bacteria from surviving. In recent years nitroimidazoles have been the subject of a great deal of research, with pretomanid and delamanid being the latest to be approved for eliminating the multiresitant tuberculosis bacteria. These two drugs are bicyclic nitroimidazoles and clinical trials have shown very good and successful results. Based on several studies, they showed no signs of toxicity in humans and demonstrated good therapeutic results. It is necessary to explore not only their activity, but also their interaction with the other drugs used in the treatment of tuberculosis. Due to the mechanism of action of these drugs, which is based on a reduction of the nitro group by a deazaflavin-dependent nitroreductase, these new nitroimidazoles appear as a new therapeutic alternative in multidrug-resistant infections. Although they have some differences between them, they have the same mechanism triggered by a nitroreductase. These proteins are a therapeutic target to be taken into consideration in the production of new drugs, and its continuous research is important, to create safety and efficacy in products to be made available in the market.
Description
Trabalho Final de Mestrado Integrado, CiĂȘncias FarmacĂȘuticas, 2022, Universidade de Lisboa, Faculdade de FarmĂĄcia.
Keywords
Tuberculose Multirresistente Nitroredutase Pretomanida Delamanida Mestrado integrado - 2022