Marine bacteria metabolomics: evaluation of larvicidal and cytotoxic activities of their extracts

Author(s)

Eduarda Antunes Moreira

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2022-11-04

Examining board members

Norberto Peporine Lopes; João Carlos Palazzo de Mello; Daniela Aparecida Chagas de Paula

• Advisor: Norberto Peporine Lopes

Abstract

The marine environment covers approximately 70% of the Earth\'s surface and its components develop unique metabolic and physiological capabilities, which culminate in the production of compounds with great chemical diversity and biotechnological potential. Due to this biosphere\'s greatness, most of the microorganisms that inhabit it remain unexplored. Nevertheless, thousands of substances with a broad spectrum of biological activities and outstanding medicinal properties have already been isolated from these organisms, which continue to be considered the most promising sources for the discovery of new chemical and therapeutic compounds. Considering that and the fact that, annually, millions of new cases of cancer and dengue infection are reported around the world - many of them resulting in death - the main objective of this project was to search for substances potentially active against a colon tumor cell line (HCT 116) and/or against L3 larvae of the Aedes aegypti mosquito in marine bacteria extracts. Aiming that, the metabolic profile of these bacteria was determined through the application of liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) and computational dereplication tools available on the Global Natural Products Social Molecular Networking (GNPS) platform. A total of 266 strains isolated from sediments on the coast of São Paulo state, in Antarctica and in the deep sea of southeastern Brazil, from ascidians found in Rocas Atoll and from cnidarians found in the coast of São Paulo, were used in this study. Initially, the extracts prepared from these bacteria were analyzed by HPLC-MS/MS and submitted to biological assays to test the biological activities of interest. The results obtained from the biological assays show that 19% of the analyzed extracts showed larvicidal activity against Aedes aegypti, and 35% showed cytotoxic activity against the colon tumor cell line. In the chemical analysis of the larvicidal strains, a relationship between the taxonomy and the chemical profile of microorganisms collected in the same region was observed, in addition to the presence of potentially active compounds belonging to different chemical classes, especially lipopeptides and terpenes. In the search for cytotoxic compounds, it was possible to reaffirm the importance of indolecarbazole derivatives, with the observation of known and commonly observed structures, such as staurosporine, and less studied derivatives, such as holyrines, in extracts considered active. The analysis of the strains relatively to their collection sites indicated that the geographic origin of the microorganisms can also interfere with their metabolic profile. Finally, the GNPS tools indicated a great diversity of secondary metabolites produced by the studied strains, pointing to the predominance of steroidal compounds and cyclic peptides among the observed chemical classes. (AU)

• FAPESP's process: 19/03008-9 - Chemical investigation on marine actinomycetes extracts with potential cytotoxic activity in tumoral lines and insecticide activity on Aedes aegypti species
• Grantee: Eduarda Antunes Moreira
• Support Opportunities: Scholarships in Brazil - Doctorate