Molecular-networking-based characterization of cytotoxic metabolites produced by the cyanobacterium Nostoc edaphicum CCNP1411
- 1Department of Marine Biology and Biotechnology, Faculty of Oceanography and Geography, University of Gdansk, Marsz. J. Piłsudskiego 46, 81378 Gdynia, Poland
- 2Department of Marine Chemistry and Biochemistry, Institute of Oceanology, Polish Academy of Sciences, Powstanców Warszawy 55, 81712 Sopot, Poland
- 3Department of Molecular Biology, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk, Poland
Abstract
Cyanobacteria of the genus Nostoc, known for their large genomes and rich repertoire of biosynthetic gene clusters, represent a prolific source of structurally diverse secondary metabolites with diverse biological activities, including cytotoxic effects. However, the identification of bioactive compounds is often hindered by low metabolite abundance and difficulties in isolating sufficient quantities for individual testing. In this study, we investigated the cytotoxic potential of chromatographic fractions obtained from Nostoc edaphicum CCNP1411 using a combination of bioassay-guided fractionation and LC–MS/MS-based feature-based molecular networking (FBMN). Cytotoxic activity was evaluated using the MTT assay across a panel of epithelial and neuronal cancer cell lines, as well as normal human dermal fibroblasts. The most active fractions, eluted with 80–90% MeOH, exhibited broad cytotoxic effects across all tested cancer cell lines. Molecular networking analysis revealed that these fractions were dominated by lipid derivatives, including lysophospholipids, monoacylglycerols, and free fatty acids, whereas previously described peptide metabolites were distributed across all fractions and were unlikely to be the main agents responsible for the observed activity. Targeted testing of selected commercially available lipid compounds confirmed their cytotoxic effects, with lysophospholipids showing the highest potency in selected cell lines. However, dose–response analysis indicated that most compounds exhibited limited potency at lower concentrations, as reflected by relatively high IC₅₀ values. Overall, our results demonstrate that lipid constituents, previously overlooked as bioactive metabolites produced by N. edaphicum CCNP1411, contribute significantly to the cytotoxic activity of the tested fractions. The application of molecular networking enabled the prioritization of bioactive metabolites and highlights its utility in linking chemical composition with biological effects in complex cyanobacterial extracts.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11030-026-11717-w.
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BibTeX
@article{konkel2026molecularnetworkingbased,
title = {{Molecular-networking-based characterization of cytotoxic metabolites produced by the cyanobacterium Nostoc edaphicum CCNP1411}},
author = {Robert Konkel and Marta Cegłowska and Łukasz Grabowski and Wiktoria Jeleniewska and Monika Zielenkiewicz and Katarzyna Gonera and Grzegorz Węgrzyn and Hanna Mazur-Marzec},
journal = {Molecular Diversity},
year = {2026},
month = sep,
doi = {10.1007/s11030-026-11717-w},
url = {https://doi.org/10.1007/s11030-026-11717-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Molecular-networking-based characterization of cytotoxic metabolites produced by the cyanobacterium Nostoc edaphicum CCNP1411
AU - Robert Konkel
AU - Marta Cegłowska
AU - Łukasz Grabowski
AU - Wiktoria Jeleniewska
AU - Monika Zielenkiewicz
AU - Katarzyna Gonera
AU - Grzegorz Węgrzyn
AU - Hanna Mazur-Marzec
PY - 2026
DA - 2026/09/09
JO - Molecular Diversity
DO - 10.1007/s11030-026-11717-w
UR - https://doi.org/10.1007/s11030-026-11717-w
AB - Cyanobacteria of the genus Nostoc, known for their large genomes and rich repertoire of biosynthetic gene clusters, represent a prolific source of structurally diverse secondary metabolites with diverse biological activities, including cytotoxic effects. However, the identification of bioactive compounds is often hindered by low metabolite abundance and difficulties in isolating sufficient quantities for individual testing. In this study, we investigated the cytotoxic potential of chromatographic fractions obtained from Nostoc edaphicum CCNP1411 using a combination of bioassay-guided fractionation and LC–MS/MS-based feature-based molecular networking (FBMN). Cytotoxic activity was evaluated using the MTT assay across a panel of epithelial and neuronal cancer cell lines, as well as normal human dermal fibroblasts. The most active fractions, eluted with 80–90% MeOH, exhibited broad cytotoxic effects across all tested cancer cell lines. Molecular networking analysis revealed that these fractions were dominated by lipid derivatives, including lysophospholipids, monoacylglycerols, and free fatty acids, whereas previously described peptide metabolites were distributed across all fractions and were unlikely to be the main agents responsible for the observed activity. Targeted testing of selected commercially available lipid compounds confirmed their cytotoxic effects, with lysophospholipids showing the highest potency in selected cell lines. However, dose–response analysis indicated that most compounds exhibited limited potency at lower concentrations, as reflected by relatively high IC₅₀ values. Overall, our results demonstrate that lipid constituents, previously overlooked as bioactive metabolites produced by N. edaphicum CCNP1411, contribute significantly to the cytotoxic activity of the tested fractions. The application of molecular networking enabled the prioritization of bioactive metabolites and highlights its utility in linking chemical composition with biological effects in complex cyanobacterial extracts. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11030-026-11717-w.
SN - 1381-1991
SN - 1573-501X
ER -