ABSTRACT
Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. We tested 62 cyanobacterial strains isolated from various Brazilian biomes for antileukemic and antimicrobial activities. Extracts from 39 strains induced selective apoptosis in acute myeloid leukemia (AML) cancer cell lines. Five of these extracts also exhibited antifungal and antibacterial activities. Chemical and dereplication analyses revealed the production of nine known natural products. Natural products possibly responsible for the observed bioactivities and five unknown, chemically related chlorinated compounds present only in Brazilian cyanobacteria were illustrated in a molecular network. Our results provide new information on the vast biosynthetic potential of cyanobacteria isolated from Brazilian environments.
Subject(s)
Anti-Infective Agents/pharmacology , Antineoplastic Agents/pharmacology , Biological Products/pharmacology , Cyanobacteria/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/isolation & purification , Antifungal Agents/pharmacology , Antineoplastic Agents/isolation & purification , Biological Products/chemistry , Brazil , Cell Line, Tumor , Cyanobacteria/classification , Cyanobacteria/genetics , Drug Discovery , Drug Screening Assays, Antitumor , Gene Regulatory Networks , Humans , Leukemia, Myeloid, Acute/drug therapy , Microbial Sensitivity TestsABSTRACT
Neoglaziovia variegata is endemic to northeastern Brazil. The drought resistant plant produces edible fruits and is used as a fibre plant by rural communities in the Caatinga region where a variety of products are made from the white, soft and flexible fibres. Extracts of N. variegata have been reported to be of low toxicity and to exhibit antinociceptive effect, photoprotective potential, antioxidant effect, gastroprotective effects and antibacterial effect against both Gram-positive and Gram-negative bacteria, however, the chemical constituents of this species are mainly unknown. The novel poly-oxygenated flavone glucoside 5,6,7,4'-tetrahydroxy-3',5'-dimethoxy-flavone 7-O-ß-glucopyranoside in addition to the rare poly-oxygenated flavone 5,4'-dihydroxy-6,7,3'-trimethoxyflavone 4'-O-ß-glucopyranoside and the flavonol quercetin 3-O-(6''-rhamnopyranosyl-ß-glucopyranoside) have been characterised from the leaves of N. variegata. 5,6,7,4'-tetrahydroxy-3',5'-dimethoxy-flavone, which comprises the core structure of the novel compound, is a new flavonoid aglycone in nature. The structure determinations were based on extensive use of 2D NMR spectroscopic techniques and high-resolution mass spectrometry. Both substances exhibited toxicity towards MOLM-13 acute myeloid leukaemia cells.