WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Conference Object Citation - WoS: 1The Effects of Novel Telomerase Activators on Human Adipose-Derived Mesenchymal Stem Cell (had-Msc) Proliferation and Osteogenic Differentiation(Georg Thieme Verlag Kg, 2022) Kuru, G.; Küçüksolak, Melis; Pulat, G.; Karaman, O.; Bedir, Erdal[No Abstract Available]Conference Object Citation - WoS: 1Phytochemical Studies on Mastic Gum of Pistacia Lentiscus Var. Chia Collected From Karaburun Peninsula and Neuroprotective Activities of the Isolates(Georg Thieme Verlag, 2022) Demir, Mehmet; Üner, Göklem; Mu, Kurt; Aygün, M.; Ballar Kırmızıbayrak, Petek; Bedir, Erdal[No Abstract Available]Article Citation - WoS: 12Citation - Scopus: 12Isolation of Rosmarinic Acid and Methyl Rosmarinate as Lipoxygenase Inhibitors From Salvia Palaestina Benth. by Activity-Guided Fractionation(Elsevier, 2021) İçen, Mehmet Sina; Gürbüz, İlhan; Bedir, Erdal; Günbatan, Tuğba; Demirci, FatihSalvia palaestina aqueous and methanol extracts were prepared from the aerial parts, which were evaluated for the in vitro anti-inflammatory properties using the lipoxygenase (LO) enzyme inhibition assay. While the aqueous extract showed no activity at test concentrations, a significant (p < 0.001) lipoxygenase inhibition was detected for the methanol extract with 29% inhibition. Activity guided fractionation was carried out on the methanol extract via liquid-liquid partitioning using n-hexane, dichloromethane, ethyl acetate, and n-butanol. The ethyl acetate fraction showed statistically the best inhibition among the sub-fractions with 70% inhibition (p < 0.0001). The compounds responsible for the activity were purified, and their structures were established as rosmarinic acid, and methyl rosmarinate by spectroscopic methods. IC50 values of rosmarinic acid, and methyl rosmarinate were calculated as 0.21 and 0.02 ?M, respectively. In conclusion, the in vitro anti-inflammatory potential of S. palaestina was associated to rosmarinic acid, and methyl rosmarinate, for the first time to the best of our knowledge. © 2021 SAABArticle 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 EuropeConference 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 Bioassay Guided Isolation of Naphthoquinones From Onosma Aksoyii, Investigation of Their Cytotoxic Properties(Georg Thieme Verlag, 2019) Kul, Demet; Karakoyun, Çiğdem; Yılmaz, Sinem; Pirhan, Ademi Fahri; Bedir, ErdalThe 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 Semi-Synthetic Studies on Astragaloside Vii and Immunomodulatory Activities of the Derivatives(Georg Thieme Verlag, 2019) Yakuboğulları, Nilgün; Sağ, Duygu; Çağır, Ali; Bedir, ErdalAdjuvants have been used in vaccine sector since 1920s to increase the immunogenicity of antigens, reduce the dosage and minimize frequency of immunizations [1]. The use of saponins as adjuvant in the prophylactic/therapeutic human and veterinary vaccines, and investigation of their immunomodulatory activities have gained importance in recent years [2],[3]. Astragaloside VII (AST VII), a triterpenoid saponin isolated from Astragalus species, stimulates Th1 mediated immune response, antigen-specific antibody response and splenocyte proliferation.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.Conference Object A New Semi-Synthetic Sapogenol Derivative Inducing Regulated Necrosis(Georg Thieme Verlag, 2019) Üner, Göklem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalSince saponin’s antitumor potency is relatively weak, researchers focus on their semi-synthetic modification to obtain structures with higher potencies. With the same motivation, we prepared a cytotoxic sapogenol derivative (AG-08) from cycloastragenol. Our preliminary studies revealed that AG-08 induced primarily necrotic cell death along with autophagic inhibition. Furthermore, immunoblotting experiments demonstrated that AG-08 promoted cleavage of various proteins such as ATGs, p62, and PARP-1.Conference Object Citation - WoS: 1Telomerase Activators Derived From Astragalus Sapogenins Via Biotransformation With the Recently Discovered Endophytic Fungus Camarosporium Laburnicola(Georg Thieme Verlag, 2019) Küçüksolak, Melis; Ekiz, Güner; Duman, Seda; Yılmaz, Sinem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalTelomeres 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.