Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
Browse
Search Results
Article Citation - WoS: 5Citation - Scopus: 5Screening of Cytotoxicity and Dna Topoisomerase Iia Inhibitory Activity of Turkish Onosma Species(TÜBİTAK, 2021) Güzel, Özge; Duman, Seda; Yılmaz, Sinem; Karakoyun, Çiğdem; Kul, Demet; Pirhan, Ademi Fahri; Bedir, ErdalOnosma L., the largest genus of Boraginaceae, is represented by 105 species in Turkey with an endemism rate of 52%. Phytochemical studies indicate that Boraginaceae plants mainly comprise naphthoquinones with a wide range of biological activities including anticancer, antiinflammatory, wound healing, and antioxidant effects. However, few taxa of the genus Onosma have been investigated in detail for their bioactivities. Considering the high rate of endemism and an inadequate number of bioactivity screening studies in literature, we aimed to evaluate the cytotoxic effects and topoisomerase inhibitory activities of some Onosma species growing in southwestern Turkey. Here, we describe a comprehensive cytotoxic activity screening study on petroleum ether, dichloromethane, and methanol extracts of the roots of 20 identified and one unidentified Onosma taxa. The MTT cell viability assay has been performed to investigate the cytotoxicity of the extracts against seven cancer cell lines (MCF-7, HeLa > Hep G2, A549, Capan-1, HCC-1937, and DU-145) and a noncancerous cell line (MRC-5), while doxorubicin was served as a positive standard. The petroleum ether extracts of O. aksoyii Aytac&Turkmen, O. isaurica Boiss. and Heldr., O. taurica Pallas ex Willd. var. taurica and O. alborosea Fisch. & C.A. Mey subsp. alborosea var. alborosea were determined as the most active ones based on their IC50 values. DNA topoisomerase Ila inhibition assay was conducted on the petroleum ether and dichloromethane extracts of these four active species, and almost all tested extracts demonstrated strong inhibition on the enzyme at a concentration of 0.1 mg/mL. Our cytotoxicity screening results were consistent with the findings of the topoisomerase Ila inhibition test. This study advocates the significant role of Onosma species in the field of anticancer drug discovery.Article Citation - WoS: 12Citation - Scopus: 12New Cardenolides From Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria Eureka 1e1bl1: Characterization and Cytotoxic Activities(MDPI, 2021) Bedir, Erdal; Karakoyun, Çiğdem; Doğan, Gamze; Kuru, Gülten; Küçüksolak, Melis; Yusufoğlu, HasanMicrobial 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.Article Citation - WoS: 5Citation - Scopus: 7Five New Cardenolides Transformed From Oleandrin and Nerigoside by Alternaria Eureka 1e1bl1 and Phaeosphaeriasp. 1e4cs-1 and Their Cytotoxic Activities(Elsevier Ltd., 2021) Karakoyun, Çiğdem; Küçüksolak, Melis; Bilgi, Eyüp; Doğan, Gamze; Çömlekçi, Yiğit Ege; Bedir, ErdalBiotransformation of oleandrin (1) and nerigoside (2) by endophytic fungi; Alternaria eureka 1E1BL1 and Phaeospheria sp. 1E4CS-1, has led to the isolation of five new metabolites (3, 5, 6, 7 and 8) together with a known compound (4). The structures of the biotransformation products were elucidated by 1D-, 2D NMR and HR-MS. Phaeospheria sp. mainly provided monooxygenation reactions on the A and B rings, whereas A. eureka afforded both monooxygenated and desacetylated derivatives of the substrates. Cytotoxic activity of the compounds was tested against a non-cancerous (HEK-293) and four cancer (PANC-1, MIA PaCa-2, DU 145 and A549) cell lines by MTT cell viability assay. All compounds were less cytotoxic than oleandrin, which had IC50 values ranging between 2.7 and 41.9 nM. Two of the monohydroxylated metabolites, viz. 7(?)-hydroxy oleandrin (3) and 1(?)-hydroxy oleandrin (7), were also potent with IC50 values from 18.45 to 39.0 nM, while desacetylated + monohydroxylated, or dihydroxylated products had much lower cytotoxicity. Additionally, the lesser activity of 2 and its metabolite (6) possessing diginose as sugar residue inferred that oleandrose moiety is important for the toxicity of oleandrin as well as hydrophobicity of the steroid core. © 2020 Phytochemical Society of Europe