Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 4Citation - Scopus: 5Identification of a Noncanonical Necrotic Cell Death Triggered Via Enhanced Proteolysis by a Novel Sapogenol Derivative(American Chemical Society, 2020) Üner, Göklem; Bedir, Erdal; Tağ, Özgür; Üner, Göklem; Erzurumlu, Yalçın; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringSmall molecules which activate distinct cell death pathways have promising high potential for anticancer drug research. Especially, regulated necrosis draws attention as an alternative cell death mechanism to overcome the drug resistance. Here, we report that a new semisynthetic saponin analogue (AG-08) triggers necrotic cell death with unprecedented pathways. AG-08-mediated necrosis depends on enhanced global proteolysis involving calpains, cathepsins, and caspases. Moreover, AG-08 generates several alterations in lysosomal function and physiology including membrane permeabilization, redistribution toward the perinuclear area, and lastly excessive tubulation. As a consequence of lysosomal impairment, the autophagic process was abolished via AG-08 treatment. Collectively, in addition to its ability to induce necrotic cell death, which makes AG-08 a promising candidate to cope with drug resistance, its unique activity mechanisms including autophagy/lysosome impairment and enhancement of proteolysis leading a strong death capacity emphasizes its potential for anticancer drug research. ©Article Citation - WoS: 23Citation - Scopus: 22Microbial Transformation of Cycloastragenol and Astragenol by Endophytic Fungi Isolated From Astragalus Species(American Chemical Society, 2019) Ekiz, Güner; Bedir, Erdal; Yılmaz, Sinem; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyBiotransformation of Astragalus sapogenins (cycloastragenol (1) and astragenol (2)) by Astragalus species originated endophytic fungi resulted in the production of five new metabolites (3, 7, 10, 12, 14) together with 10 known compounds. The structures of the new compounds were established by NMR spectroscopic and HRMS analysis. Oxygenation, oxidation, epoxidation, dehydrogenation, and ring cleavage reactions were observed on the cycloartane (9,19-cyclolanostane) nucleus. The ability of the compounds to increase telomerase activity in neonatal cells was also evaluated. After prescreening studies to define potent telomerase activators, four compounds were selected for subsequent bioassays. These were performed using very low doses ranging from 0.1 to 30 nM compared to the control cells treated with DMSO. The positive control cycloastragenol and 8 were found to be the most active compounds, with 5.2- (2 nM) and 5.1- (0.5 nM) fold activations versus DMSO, respectively. At the lowest dose of 0.1 nM, compounds 4 and 13 provided 3.5- and 3.8-fold activations, respectively, while cycloastragenol showed a limited activation (1.5-fold).Article Citation - WoS: 20Citation - Scopus: 24Biotransformation of Neoruscogenin by the Endophytic Fungus Alternaria Eureka(American Chemical Society, 2018) Özçınar, Özge; Bedir, Erdal; Tağ, Özgür; Yusufoğlu, Hasan; Kıvçak, Bijen; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyBiotransformation of neoruscogenin (NR, 1, spirosta-5,25(27)-diene-1β,3β-diol), the major bioactive sapogenin of Ruscus preparations, was carried out with the endophytic fungus Alternaria eureka. Fourteen new biotransformation products (2-15) were isolated, and their structures were elucidated by NMR and HRESIMS data analyses. A. eureka affected mainly oxygenation, oxidation, and epoxidation reactions on the B and C rings of the sapogenin to afford compounds 8-15. In addition to these, cleavage of the spiroketal system as in compounds 2-7 and subsequent transformations provided unusual metabolites. This is the first study reporting conversion of the spirostanol skeleton to cholestane-type metabolites 2-5. Additionally, the cleavage of the C-22/C-26 oxygen bridge yielding a furostanol-type steroidal framework and subsequent formation of the epoxy bridge between C-18 and C-22 in 7 was encountered for the first time in steroid chemistry.