Monitoring antibiotics in the environment. Study of Quinoxaline derivatives bioactivity

• Author(s): Vieira, Mónica Andreia Almeida
• Date: 2013
• Persistent ID: http://hdl.handle.net/10362/11350
• Origin: Repositório Institucional da UNL
• Subject(s): Antimicrobials; Environment; Food; Antimicrobial resistance; Quinoxalines
• Document Type: Doctoral thesis
• Language: English
• Advisor(s): Noronha, João; Soares, Maria Cristina; Rodrigues, Célia
• Contributor(s): RUN

Description

Dissertação para obtenção do Grau de Doutor em Química Sustentável

Antimicrobial agents have revolutionized medicine and promoted an increase in average life expectancy of human populations worldwide. These drugs are used not only in human medicine but also in veterinary practice, in the treatment and prevention of infections, and in some regions in the world, as well as growth promoters, ensuring a greater and better animal production. The use of antimicrobial agents in animal production causes contamination of the final product with drug residues that are eventually distributed in human food chain. Residues of antimicrobial agents provenient from human and animal consumption are also present in sewage, surface water or ground water. It is still unknown all the consequences of this contamination, but there are indications of changes in indigenous microbiota. The use of these drugs was quickly followed by the emergence of resistance, which led to decreased efficacy and compounds available. Therefore, the spread of antimicrobial agents in the environment is also associated with increased resistance to such drugs. The presented work intended to establish methods for monitoring the presence of antibiotics in animal foods, evaluate if the presence of antimicrobial agents in the environment at sub-inhibitory concentrations can contribute to the selection of resistant bacteria and characterize the biological activity of a number of compounds of the quinoxaline family as potential new antimicrobial agents. In order to achieve these objectives, chromatographic techniques were used for detection and quantification of antimicrobial agents, methods of microbiology and molecular biology to evaluate the behavior of bacteria under selective pressure. Various strains of prokaryotes and eukaryotes microorganisms were also used to evaluate the antimicrobial activity of N-oxide derivatives of quinoxaline. We used, also, cell cultures to assess the potential toxicity of these new antibiotics. A new chromatographic method was developed to quantify the reduced and oxidized forms of glutathione, in order to infer the cellular oxidative stress induced by exposure to the quinoxaline derivative compounds with proven antimicrobial activity. The results confirm that the chromatographic HPLC-DAD methods are powerful tools in monitoring food quality. They also indicate that the presence of subinhibitory amounts of ciprofloxacin in water may influence the dynamic of susceptible and resistant to ciprofloxacin Escherichia coli population. An assessment of the biological activity of quinoxaline derivatives indicated the compounds studied as potential new antimicrobial agents who have shown low toxicity in cell lines and oxidative cell damage in small extent.

Fundação para a Ciência e Tecnologia - bolsa de doutoramento SFRH / BD /48116 / 2008