Microscale dereplication to expedite the discovery of natural products from cyanobacteria

Abstract

Cyanobacteria are microorganisms that produce diverse secondary metabolites with biological activity. However, the search for new cyanobacterial natural products faces challenges due to the complexity of extracts and the time required for bioassay-guided fractionation cycles. This project aims to accelerate and optimize the process of discovering cyanobacterial natural products with potential pharmaceutical applications by implementing a microscale dereplication strategy. Brazilian cyanobacterial strains will be cultured, and their biomass will be extracted, prefractionated, and screened for antibiotic and antiproliferative activities. Bioactive fractions will undergo a secondary fractionation by HPLC. Subfractions will be tested in bioassays and subjected to dereplication using a combination of mass spectrometry, nuclear magnetic resonance spectroscopy, metabolomic analyses, and database searches. Compounds identified as potentially novel and bioactive will be isolated and will have their structures elucidated. We expect that microscale dereplication will expedite the process of natural product drug discovery from Brazilian cyanobacteria.