ESTUDO DO MECANISMO DE AÇÃO ANTIBIÓTICA DE ω-AMINOALCOXILXANTONAS SOBRE S. aureus UTILIZANDO ANÁLISE METABOLÔMICA POR RMN E QUIMIOMETRIA

• Ano de defesa: 2022
• Autor(a) principal: PAOLA DIAS DE OLIVEIRA
• Orientador(a): Ana Camila Micheletti
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Fundação Universidade Federal de Mato Grosso do Sul
• País: Brasil
• Palavras-chave em Português: mecanismo de ação antibacteriana; xantonas; metaboloma; RMN; docking molecular.
• Link de acesso: https://repositorio.ufms.br/handle/123456789/4765

Due to the resistance that some bacteria acquire to drugs, it is essential to use analytical techniques to identify the mechanism of action of substances that have the potencial to act as antibacterials. In this regard, NMR-based metabolomics has become a powerful alternative to provide important answers on the bacterial structure and to support the understanding about mode of action of antibiotics on bacterial structure using the bacterial metabolic changes. In our study, NMR was use to investigate the metabolic responses of one S. aureus strains against four antibiotics with different modes of action and three synthesized substances from xanthone class. We observed by chemometric analysis a distinction between control group and antibiotics with extracellular targets, such as ampicillin, and intracellular targets, such as kanamycin, tetracycline and ciprofloxacin. From the chemical profile of the metabolites, we identified that the amino acids and important precursors to differentiate the groups were betaine, acetamide, glutamate, lysine, alanine, isoleucine/leucine, acetate, threonine, proline and ethanol. Thus, we verified a strong tendency for the S6, S7 and S8 (xanthonic derivatives) group to be similar to the ciprofloxacin group, which target bacterial DNA replication. The molecular docking analysis of the compounds synthesized with the active site of the topoisomerase IV enzyme, the target enzyme of ciprofloxacin, the target enzyme of ciprofloxacin, which showed a high affinity of substances S6, S7 and S8 with the enzyme topoisomerase IV, consolidating the results obtained in the chemometric analysis. Therefore, NMR-based metabolomics proved to be a useful technique to access the metabolic profile of S. aureus after some treatment with substances that have antimicrobial activity, helping us to investigate the mechanism of action of the synthesized substances.