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Abstract(s)
O presente relatório encontra-se dividido em três capítulos. O primeiro capítulo é
referente ao trabalho na componente de investigação em Ciências Farmacêuticas,
desenvolvido no Departamento de Química e no CICS-UBI - Centro de Investigação em
Ciências da Saúde da Universidade da Beira Interior e envolve a síntese química de
compostos híbridos de iminodibenzilo com quinolonas e à avaliação da sua atividade
antibacteriana.
O abuso e o uso inapropriado de antibióticos levou ao desenvolvimento e seleção de
bactérias resistentes aos mesmos. Uma das formas de resistência aos antibióticos
envolve o efluxo ativo destes fármacos da célula bacteriana através de bombas de
efluxo. Este é um dos mecanismos conhecidos de resistência às quinolonas, conhecidos
agentes antibacterianos. Uma forma de contrariar este tipo de resistência pode passar
pelo uso de inibidores de bombas de efluxo. Alguns fármacos comercializados
demonstraram a capacidade de inibir os sistemas de efluxo, como é o caso do
antidepressivo tricíclico, amitriptilina. O iminodibenzilo é um sistema tricíclico
semelhante encontrado na estrutura de alguns antidepressivos tricíclicos, como a
imipramina. Assim, este estudo teve como objetivo sintetizar moléculas híbridas de
iminodibenzilo e quinolonas com atividade antibacteriana contra bactérias com
resistência às quinolonas mediada por efluxo, através da inibição das suas bombas de
efluxo. Para isso, dois compostos precursores (2-cloro-1-(10,11-dihidro-5Hdibenzo[b,f]azepin-5-il)etanona e 3-cloro-1-(10,11-dihidro-5H-dibenzo[b,f]azepin-5-il)-
1-propanona) foram produzidos. Seguidamente, híbridos de ciprofloxacina e de
norfloxacina foram sintetizados usando cada um desses precursores, os quais foram
caracterizados por espectroscopia de infravermelhos e de ressonância magnética
nuclear (RMN). Posteriormente, a atividade antibacteriana de dois híbridos e de ambos
os precursores foi avaliada numa estirpe nativa e numa estirpe de Staphylococcus
aureus que sobreexpressa NorA, bem como numa estirpe nativa de Escherichia coli e
sua correspondente sobreexpressando o sistema AcrAB-toIC, pela determinação da
concentração inibitória mínima (CIM) pelo método de microdiluição. Ambos os
híbridos mostraram atividade antibacteriana promissora contra S. aureus que
sobreexpressa a bomba de efluxo NorA, tendo sido determinada uma CIM mais baixa
para ambos os híbridos do que para os antibióticos, ciprofloxacina e norfloxacina. Em
suma, este trabalho demonstra a ação antibacteriana de híbridos de quinolonas com
inibidores de sistemas de efluxo sintetizados a partir de iminodibenzilo com fluoroquinolonas contra uma bactéria com resistência a antibióticos mediada por
efluxo.
O segundo capítulo relata a experiência no estágio em farmácia comunitária efetuado
na Farmácia Diamantino entre 10 de fevereiro a 29 de abril de 2022, sob orientação da
Farmacêutica Substituta Drª Natália Oliveira. Neste estão apresentadas as áreas de
intervenção de um farmacêutico comunitário como o atendimento ao público, ações na
comunidade e gestão de uma farmácia.
O terceiro capítulo diz respeito ao estágio em farmácia hospitalar decorrido nos
serviços farmacêuticos do Centro Hospitalar e Universitário Cova da Beira entre 2 de
maio e 17 de junho de 2022 sob a orientação da Doutora Olímpia Fonseca. Neste
capítulo encontram-se descritas as diversas áreas em que atua um farmacêutico
hospitalar, nomeadamente a gestão e logística do serviço, os diversos modos
distribuição do medicamento, farmacotecnia e outras funções desempenhadas no
âmbito de uma equipa multidisciplinar num hospital.
This report is divided into three chapters. The first chapter refers to the work in the research component in Pharmaceutical Sciences, developed at the Department of Chemistry and at the CICS-UBI - Health Sciences Research Centre of the University of Beira Interior, concerning the chemical synthesis of hybrid compounds of quinolone with iminodibenzyl and the evaluation of their antibacterial activity. The abuse and inappropriate use of antibiotics has led to the development and selection of drug-resistant bacteria. One of the forms of antibiotic resistance arises from the active efflux of drugs from the bacterial cell through efflux pumps. This is one of the known resistance mechanisms to the antibacterial agents, quinolones. One way to counteract this type of resistance is to use efflux pump inhibitors. Some commercialized drugs have demonstrated the ability to inhibit the efflux pump systems, as is the case of the tricyclic antidepressant amitriptyline. Iminodibenzyl is a similar tricyclic system found in the structure of some tricyclic antidepressants, such as imipramine. Thus, this study aimed to synthesize hybrid molecules of iminodibenzyl and quinolones with antibacterial activity against efflux-mediated quinolone resistance bacteria by inhibiting their efflux pumps. Firstly two precursor compounds (2-chloro-1- (10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethanone and 3-chloro-1-(10,11-dihydro5H-dibenzo[b,f]azepin-5-yl)-1-propanone) were produced. Afterwards ciprofloxacin and norfloxacin hybrids were synthesized using each of these precursors, which were characterized by infrared and nuclear magnetic resonance (NMR) spectroscopy. Subsequently, the antibacterial activity of two hybrids and both precursors was evaluated by determination of the minimum inhibitory concentration (MIC) by the broth microdilution method on the wildtype and NorA-overexpressing Staphylococcus aureus, as well as for a wildtype and a AcrAB-toIC overexpressing Escherichia coli. Both hybrids have shown promising antibacterial activity against the NorA efflux pump overexpressing S. aureus, where a lower MIC was determined for both hybrids than for the antibiotics, ciprofloxacin and norfloxacin. In sum, this work demonstrates the antibacterial action of efflux pump inhibitors hybrids synthesized from iminodibenzil with fluoroquinolones against a strain of efflux-mediated antibiotic resistance bacteria. The second chapter reports the experience in the community pharmacy internship carried out at Farmácia Diamantino between February 10th and April 29th, 2022, under the guidance of Substitute Pharmacist Dr. Natália Oliveira. This chapter presents the areas of intervention of a community pharmacist, such as customer service, actions in the community and management of a pharmacy. The third chapter concerns the internship in hospital pharmacy that took place in the pharmaceutical services of the Centro Hospitalar e Universitário Cova da Beira between May 2nd and June 17th, 2022, under the guidance of Dr. Olímpia Fonseca. This chapter describes the various areas in which a hospital pharmacist operates, namely the management and logistics of the service, the different modes of drug distribution, pharmacotechnics and other functions performed within the scope of a multidisciplinary team in a hospital.
This report is divided into three chapters. The first chapter refers to the work in the research component in Pharmaceutical Sciences, developed at the Department of Chemistry and at the CICS-UBI - Health Sciences Research Centre of the University of Beira Interior, concerning the chemical synthesis of hybrid compounds of quinolone with iminodibenzyl and the evaluation of their antibacterial activity. The abuse and inappropriate use of antibiotics has led to the development and selection of drug-resistant bacteria. One of the forms of antibiotic resistance arises from the active efflux of drugs from the bacterial cell through efflux pumps. This is one of the known resistance mechanisms to the antibacterial agents, quinolones. One way to counteract this type of resistance is to use efflux pump inhibitors. Some commercialized drugs have demonstrated the ability to inhibit the efflux pump systems, as is the case of the tricyclic antidepressant amitriptyline. Iminodibenzyl is a similar tricyclic system found in the structure of some tricyclic antidepressants, such as imipramine. Thus, this study aimed to synthesize hybrid molecules of iminodibenzyl and quinolones with antibacterial activity against efflux-mediated quinolone resistance bacteria by inhibiting their efflux pumps. Firstly two precursor compounds (2-chloro-1- (10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethanone and 3-chloro-1-(10,11-dihydro5H-dibenzo[b,f]azepin-5-yl)-1-propanone) were produced. Afterwards ciprofloxacin and norfloxacin hybrids were synthesized using each of these precursors, which were characterized by infrared and nuclear magnetic resonance (NMR) spectroscopy. Subsequently, the antibacterial activity of two hybrids and both precursors was evaluated by determination of the minimum inhibitory concentration (MIC) by the broth microdilution method on the wildtype and NorA-overexpressing Staphylococcus aureus, as well as for a wildtype and a AcrAB-toIC overexpressing Escherichia coli. Both hybrids have shown promising antibacterial activity against the NorA efflux pump overexpressing S. aureus, where a lower MIC was determined for both hybrids than for the antibiotics, ciprofloxacin and norfloxacin. In sum, this work demonstrates the antibacterial action of efflux pump inhibitors hybrids synthesized from iminodibenzil with fluoroquinolones against a strain of efflux-mediated antibiotic resistance bacteria. The second chapter reports the experience in the community pharmacy internship carried out at Farmácia Diamantino between February 10th and April 29th, 2022, under the guidance of Substitute Pharmacist Dr. Natália Oliveira. This chapter presents the areas of intervention of a community pharmacist, such as customer service, actions in the community and management of a pharmacy. The third chapter concerns the internship in hospital pharmacy that took place in the pharmaceutical services of the Centro Hospitalar e Universitário Cova da Beira between May 2nd and June 17th, 2022, under the guidance of Dr. Olímpia Fonseca. This chapter describes the various areas in which a hospital pharmacist operates, namely the management and logistics of the service, the different modes of drug distribution, pharmacotechnics and other functions performed within the scope of a multidisciplinary team in a hospital.
Description
Keywords
Farmácia Comunitária Farmácia Hospitalar Inibidores de Bombas de Efluxo Quinolonas Resistência Bacteriana