Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Conference Object Short Lecture "method Development for Pilot Production of Astragaloside Vii"(Georg Thieme Verlag, 2022) Kurt, Mustafa Ünver; Tağ, Özgür; Bedir, ErdalBased on the promising immunostimulant effect comparable to commercialized adjuvants Alum and Quillaja saponins (including QS-21) [1], [2], [3], our team has been prompted to carry out advance studies for developing Astragaloside VII (AST VII) ([Fig. 1]) as a new vaccine adjuvant or an immunotherapeutic agent. Hence, one of the most critical challenges is establishing efficient isolation and purification processes to obtain AST VII on a large scale. Thus, this study aimed to develop a production methodology for AST VII from Turkish Astragalus species.Conference Object Citation - WoS: 1Microbial Transformation of Ruscogenins by Cunninghamella Blakesleeana(Georg Thieme Verlag, 2016) Özçınar, Özge; Tağ, Özgür; Kıvçak, Bijen; Bedir, ErdalThe natural product drug discovery process involves the isolation of new molecules from natural sources, investigation of their biological activities, and semi-synthesis of more active analogs. Microbial transformation plays a vital role in the preparation of new oxygenated derivatives, and has frequently been used as microbial model of mammalian drug metabolism [1,2]. It has been proved that the hydroxylation of steroidal compounds is catalyzed by cytochrome P450 monoxygenase systems, which exist in all eucaryotic microorganisms [3]. Cunninghamella genus has been widely used in transformation of steroids [4,5]. The major steroidal saponins of Ruscus aculeatus, ruscogenin and neoruscogenin, has strong anti-inflammatory activities, acts as an anti-elastase, and decreases capillary permeability [6]. In the present study microbial transformation of Neoruscogenin:Ruscogenin (78:22) mixture by Cunninghamella blakesleeana fungus afforded three new compounds. The structures were elucidated by LC-MS, 1D- and 2D NMR analyses as shown below. Mainly oxydation products were obtained from neoruscogenin by C. blakesleana. As far as can be ascertained from the literature, this is the first microbial transformation study performed on neoruscogenin.Conference Object A Validated Uhplc-Cad Method for Quantitative Determination of Astragaloside Vii(Georg Thieme Verlag, 2019) Kurt, Mustafa Ünver; Tağ, Özgür; Bedir, ErdalAstragaloside VII (AST VII) [Fig 1], the first tridesmosidic saponin identified in nature [1], possesses potent immunostimulatory/adjuvant effects [2]. Based on the promising adjuvant properties comparable to current adjuvants (i.e. Alum and QS-21), our team has decided to carry out further studies on AST VII including semi-synthesis studies to discover and develop new human/animal vaccine adjuvants [2]–[5]. Since more than 450 Astragalus species grow wildly in Turkish flora, one of the first challenges of this adjuvant development project is to examine these species by efficient analytical methods to find AST VII rich plant materials and select the rich species for possible cultivation and/or pilot production studies. Thus, aim of this study was to develop a UHPLC method coupled with the Charged Aerosol Detector (CAD) in order to determine AST VII content simultaneously, precisely and sensitively in Astragalus samples. A fifteen minutes method was developed using C18 (100 mm x 4 mm x 3 µm) column, eluting with gradient Water:Acetonitrile mixtures at 0.75 mL/min flow rate. The linear regression analysis of calibration plots showed good linear relationship with r 2=0.9995 in concentrations ranging from 52 to 208 μg/mL. The method was validated for its calibration curve, specificity, precision and robustness. The recovery was found to be in the range of 98.17 to 101.86%. As a conclusion, for the first time, a UHPLC method was validated to quantify AST VII utilizing CAD for its detection.Article Citation - WoS: 13Citation - Scopus: 13Cycloartane-Type Sapogenol Derivatives Inhibit Nf?b Activation as Chemopreventive Strategy for Inflammation-Induced Prostate Carcinogenesis(Elsevier Ltd., 2018) Debeleç Bütüner, Bilge; Öztürk, Mert Burak; Tağ, Özgür; Akgün, İsmail Hakkı; Yetik Anacak, Günay; Bedir, Erdal; Korkmaz, Kemal SamiChronic inflammation is associated to 25% of cancer cases according to epidemiological data. Therefore, inhibition of inflammation-induced carcinogenesis can be an efficient therapeutic approach for cancer chemoprevention in drug development studies. It is also determined that anti-inflammatory drugs reduce cancer incidence. Cell culture-based in vitro screening methods are used as a fast and efficient method to investigate the biological activities of the biomolecules. In addition, saponins are molecules that are isolated from natural sources and are known to have potential for tumor inhibition. Studies on the preparation of analogues of cycloartane-type sapogenols (9,19-cyclolanostanes) have so far been limited. Therefore we have decided to direct our efforts toward the exploration of new anti-tumor agents prepared from cycloastragenol and its production artifact astragenol. The semi-synthetic derivatives were prepared mainly by oxidation, condensation, alkylation, acylation, and elimination reactions. After preliminary studies, five sapogenol analogues, two of which were new compounds (2 and 3), were selected and screened for their inhibitory activity on cell viability and NFκB signaling pathway activity in LNCaP prostate cancer cells. We found that the astragenol derivatives 1 and 2 as well as cycloastragenol derivatives 3, 4, and 5 exhibited strong inhibitory activity on NFκB signaling leading the repression of NFκB transcriptional activation and suppressed cell proliferation. The results suggested that these molecules might have significant potential for chemoprevention of prostate carcinogenesis induced by inflammatory NFκB signaling pathway.