Bioengineering / Biyomühendislik

Permanent URI for this collectionhttps://hdl.handle.net/11147/4529

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Access Right: Closed AccessAuthor: search.filters.author.Yılmaz, Sinem

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Now showing 1 - 5 of 5
  • Article
    Citation - WoS: 19
    Citation - Scopus: 21
    Telomerase Activators From 20(27)-Octanor Via Biotransformation by the Fungal Endophytes
    (Academic Press, 2021) Duman, Seda; Bedir, Erdal; Yılmaz, Sinem; Yusufoğlu, Hasan; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 01.01. Units Affiliated to the Rectorate; 01. Izmir Institute of Technology; 03. Faculty of Engineering
    Cycloastragenol [20(R),24(S)-epoxy-3 beta,6 alpha,16 beta,25-tetrahydroxycycloartane] (CA), the principle sapogenol of many cycloartane-type glycosides found in Astragalus genus, is currently the only natural product in the anti-aging market as telomerase activator. Here, we report biotransformation of 20(27)-octanor-cycloastragenol (1), a thermal degradation product of CA, using Astragalus species originated endophytic fungi, viz. Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae and Camarosporium laburnicola. Fifteen new biotransformation products (2-16) were isolated, and their structures were established by NMR and HRESIMS. Endophytic fungi were found to be capable of performing hydroxylation, oxidation, ring cleavage-methyl migration, dehydrogenation and Baeyer-Villiger type oxidation reactions on the starting compound (1), which would be difficult to achieve by conventional synthetic methods. In addition, the ability of the metabolites to increase telomerase activation in Hekn cells was evaluated, which showed from 1.08 to 12.4-fold activation compared to the control cells treated with DMSO. Among the compounds tested, 10, 11 and 12 were found to be the most potent in terms of telomerase activation with 12.40-, 7.89- and 5.43-fold increase, respectively (at 0.1, 2 and 10 nM concentrations, respectively).
  • Article
    Citation - WoS: 4
    A Src/Abl Kinase Inhibitor, Bosutinib, Downregulates and Inhibits Parp Enzyme and Sensitizes Cells To the DNA Damaging Agents
    (Türk Biyokimya Derneği, 2018) Kırmızıbayrak, Petek Ballar; Yılmaz, Sinem; Yılmaz, Sinem; Günal, Selin; Tepedelen, Burcu Erbaykent; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Background: Poly(ADP-ribosyl)ation (PARylation) catalyzed mainly by PARP1 is a highly regulated posttranslational modification associated with several pathways in cellular physiology and genotoxic deoxyribonucleic acid (DNA) damage response. PAR polymers and PARP enzyme function in DNA integrity maintenance and several PARP inhibitors have entered clinical phase studies for cancer therapies. Material and methods: The effect of bosutinib, a dual Src/Abl kinase inhibitor, on PARylation was fluorometrically measured. The cytotoxic and chemosensitizing effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of DNA repair proteins and PARP enzyme were examined by immunoblotting. Results: In this study, bosutinib is characterized as a novel PARP inhibitor. Bosutinib inhibited oxidative stress-induced cellular PARylation and nuclear foci formation by downregulating PARP1 levels. Bosutinib was found to be more cytotoxic on Capan1 cells with BRCA2 mutation. Furthermore by acting as a chemosensitizer, bosutinib enhanced the cytotoxicity of doxorubicin (DOXO) and etoposide (ETP) by decreasing phosphorylation of DNA repair enzymes checkpoint kinase 1 (Chk1) and ataxia-telangiectasia mutated (ATM). Conclusion: By inhibition of both PARP and DNA damage checkpoint kinases, bosutinib increased the phospho-H2AX levels, an early indicator of DNA double strand breaks.
  • Conference Object
    Bioassay Guided Isolation of Naphthoquinones From Onosma Aksoyii, Investigation of Their Cytotoxic Properties
    (Georg Thieme Verlag, 2019) Kul, Demet; Bedir, Erdal; Karakoyun, Çiğdem; Yılmaz, Sinem; Yılmaz, Sinem; Pirhan, Ademi Fahri; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    The genus Onosma L. (Boraginaceae) includes about 230 species, distributed mainly in the Mediterranean region and Central Asia. Major constituents of Onosma species are alkaloids, naphthoquinones, polyphenols, phytosterols, terpenoids and fatty acids [1], [2]. Naphthoquinones are naturally widespread secondary metabolites deriving from some higher plants, fungi and bacteria. They exhibit significant biological activities such as cytotoxicity, antimalarial, antibacterial, antifungal and wound healing [2], [3]. Recently naphthoquinone derivatives have also been recognized as potent topoisomerase inhibitors [4].
  • Conference Object
    Citation - WoS: 1
    Telomerase Activators Derived From Astragalus Sapogenins Via Biotransformation With the Recently Discovered Endophytic Fungus Camarosporium Laburnicola
    (Georg Thieme Verlag, 2019) Küçüksolak, Melis; Yılmaz, Sinem; Ekiz, Güner; Duman, Seda; Duman, Seda; Bedir, Erdal; Yılmaz, Sinem; Küçüksolak, Melis; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 01.01. Units Affiliated to the Rectorate; 01. Izmir Institute of Technology; 03. Faculty of Engineering
    Telomeres are nucleotide sequences that are located at the end of chromosomes shortening with each cell division. Telomerase is a reverse transcriptase enzyme, and it helps to replenish telomere ends that are truncated by aging and stress factors.
  • Article
    Citation - WoS: 23
    Citation - Scopus: 22
    Microbial 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 Technology
    Biotransformation 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).