Metabolômica de Caesalpinia pluviosa var. peltophoroides, fitoquímica e avaliação das atividades anti-inflamatória e antitumoral

• Ano de defesa: 2018
• Autor(a) principal: Domingos, Olívia Da Silva
• Orientador(a): Paula, Daniela Aparecida Chagas De
• Banca de defesa: Silva, Marcelo Aparecido, Vidal, Diogo Montes
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Alfenas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Química
• Departamento: Instituto de Química
• País: Brasil
• Palavras-chave em Português: Edema; Infiltração de Neutrófilos; Neoplasias; Cromatografia Líquida de Alta Pressão; Biflavonóides.
• Área do conhecimento CNPq: QUIMICA ORGANICA::QUIMICA DOS PRODUTOS NATURAIS
• Link de acesso: https://repositorio.unifal-mg.edu.br/handle/123456789/1387

The metabolomic approaches are important in the analysis of complex mixtures, since they can help avoid the isolation of substances already known and guide the isolation of target substances, such as those unpublished or correlated with some investigated property. Anti-inflammatories are among the most widely used therapeutic agents in the world, however, these drugs have several limitations regarding their potency, efficacy, and mainly adverse effects. Thus, it is necessary to search for new anti-inflammatories, prioritizing agents with innovative mechanisms of action. It is also known that the inflammatory conditions increase the risk of cancer, appearing even before the occurrence of malignant changes. Cancer is one of the leading causes of death in the world and available antitumor drugs also have limitations. The species Caesalpinia pluviosa var. peltophoroides has demonstrated significant anti-inflammatory and cytotoxic potential. In this context, the cytotoxic and anti-inflammatory activity of the hydroethanolic, ethyl acetate and hexane fractions from different parts of C. pluviosa was evaluated and, subsequently, metabolomic (HPLC-UV-HRFTMS) and in silico analysis determined the biomarkers of these pharmacological properties. Thus, the guided chromatographic process led to the isolation of two unknown methoxylated derivatives of the biflavonoid caesalpinioflavone, called 4′′′-methoxycaesalpinioflavone and 7-methoxycaesalpinioflavone, in addition to obtaining a bichalcone, rhuschalcone VI, already identified in this species. These substances promoted dual in vivo inhibition of edema and neutrophil recruitment. In addition, two of these biomarkers showed better efficacy than the reference drug. These results corroborated with those obtained statistically through metabolomic analyzes, confirming that these approaches clearly directed the isolation of substances of interest. The isolated substances were also correlated positively with cytotoxic activity against some types of tumoral cells; therefore, they should be submitted to cytotoxic assays. Thus, it was verified that the species C. pluviosa is extremely promising in the search for new substances and biomarkers of both activities evaluated.