Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/11540
Title: New cardenolides from biotransformation of gitoxigenin by the endophytic fungus alternaria eureka 1E1BL1: Characterization and cytotoxic activities
Authors: Bedir, Erdal
Karakoyun, Çiğdem
Doğan, Gamze
Kuru, Gülten
Küçüksolak, Melis
Yusufoğlu, Hasan
Keywords: Nerium oleander L.
Cardenolides
Oleandrin
Gitoxigenin
Biotransformation
Endophytic fungus
Cytotoxicity
Issue Date: 2021
Publisher: MDPI
Abstract: Microbial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; similar to 25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 mu M against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 mu M. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.
URI: https://doi.org/10.3390/molecules26103030
https://hdl.handle.net/11147/11540
ISSN: 1420-3049
Appears in Collections:Bioengineering / Biyomühendislik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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