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: 5Citation - Scopus: 6Undescribed Polyether Ionophores From Streptomyces Cacaoi and Their Antibacterial and Antiproliferative Activities(Elsevier, 2022) Gezer, Emre; Üner, Göklem; Küçüksolak, Melis; Kurt, Mustafa Ünver; Doğan, Gamze; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether ionophores represent a large group of naturally occurring compounds mainly produced by Streptomyces species. With previously proven varieties of bioactivity including antibacterial, antifungal, antiparasitic, antiviral and anti-tumor effects, the discovery of undescribed polyethers leading to development of efficient therapeutics has become important. As part of our research on polyether-rich Streptomyces cacaoi, we previously performed modification studies on fermentation conditions to induce synthesis of specialized metabolites. Here, we report four undescribed and nine known polyether compounds from S. cacaoi grown in optimized conditions. Antimicrobial activity assays revealed that four compounds, including the undescribed (6), showed strong inhibitory effects over both Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA) growth. Additionally, K41-A and its C15-demethoxy derivative exhibited significant cytotoxicity. These results signified that selectivity of C15-demethoxy K41-A towards cancer cells was higher than K41-A, which prompted us to conduct mechanistic experiments. These studies showed that this uninvestigated compound acts as a multitarget compound by inhibiting autophagic flux, inducing reactive oxygen species formation, abolishing proteasome activity, and stimulating ER stress. Consequently, the optimized fermentation conditions of S. cacaoi led to the isolation of undescribed and known polyethers displaying promising activities.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: 4Citation - Scopus: 5Identification of a Noncanonical Necrotic Cell Death Triggered Via Enhanced Proteolysis by a Novel Sapogenol Derivative(American Chemical Society, 2020) Üner, Göklem; Tağ, Özgür; Erzurumlu, Yalçın; Ballar Kırmızıbayrak, Petek; Bedir, ErdalSmall 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: 21Citation - Scopus: 21Development of Adjuvant Nanocarrier Systems for Seasonal Influenza a (h3n2) Vaccine Based on Astragaloside Vii and Gum Tragacanth (aps)(Elsevier, 2019) Yakuboğulları, Nilgün; Genç, Rukan; Coven, Fethiye; Nalbantsoy, Ayşe; Bedir, ErdalAdjuvants are chemical/biological substances that are used in vaccines to increase the immunogenicity of antigens. A few adjuvants have been developed for use in human vaccines because of their limitations including lack of efficacy, unacceptable local or systemic toxicity, the difficulty of manufacturing, poor stability, and high cost. For that reasons, novel adjuvants/adjuvant systems are under search. Astragaloside VII (AST-VII), isolated from Astragalus trojanus, exhibited significant cellular and humoral immune responses. The polysaccharides (APS) obtained from the roots of Astragalus species have been used in traditional Chinese medicine and possess strong immunomodulatory properties. In the present study, the immunomodulatory effects of a newly developed nanocarrier system (APNS: APS containing carrier) and its AST-VII containing formulation (ANS: AST-VII + APNS), on seasonal influenza A (H3N2) vaccine were investigated. Inactivated H3N2 alone or its combinations with test compounds/formulations were intramuscularly injected into Swiss albino mice. Four weeks after immunization, the immune responses were evaluated in terms of antibody and cytokine responses as well as splenocyte proliferation. APNS demonstrated Th2 mediated response by increasing IgG1 antibody titers, whereas ANS showed response towards Th1/Th2 balance and Th17 by producing of IFN-gamma, IL-17A and IgG2a. Based on these results, we propose that APNS and ANS are good candidates to be utilized in seasonal influenza A vaccines as adjuvants/carrier systems. (C) 2019 Elsevier Ltd. All rights reserved.Article Citation - WoS: 36Citation - Scopus: 38Phytochemical Screening and Evaluation of the Antimicrobial and Antioxidant Activities of Ferula Caspica M. Bieb. Extracts(King Saud University, 2019) Kahraman, Çiğdem; Topçu, Gülaçtı; Bedir, Erdal; Tatlı, İ. İrem; Ekizoğlu, Melike; Akdemir, Zeliha S.Chloroform, ethyl acetate and methanol extracts from the aerial parts of Ferula caspica M. Bieb. were tested for their antioxidant capacities by CUPRAC, ABTS, FRAP, Folin-Ciocalteu and aluminum chloride methods and for antimicrobial activities by the broth microdilution method. Chloroform and ethyl acetate extracts showed the highest antioxidant capacity and antimicrobial activity. Three known sesquiterpene derivatives; 1-(2',4'-dihydroxyphenyl)-3,7,11-trimethyl-3-vinyl-6(E), 10-dodecadien-1-one (1), 2,3-dihydro-7-hydroxy-2,3-dimethyl-2-[4',8'-dimethyl-3',7'-nonadienyl]-furo[3,2,c]coumarin (2), 2,3-dihydro-7-hydroxy-2,3-dimethyl-3-[4',8'-dimethyl-3',7'-nonadienyl]-furo[3,2,c]coumarin(3); phenylpropanoid; laserine/2-epilaserine (4/5) and steroid mixtures; stigmasterol and beta-sitosterol (6/7) were isolated from chloroform extract; three known flavonoids; kaempferol-3-O-beta-glucopyranoside (8), kaempferol-3-O-alpha-rhamnopyranoside (9), quercetin-3-O-beta-glucopyranoside (10), and one benzoic acid derivative; 2,4-dihydroxybenzoic acid (11) were isolated from the ethyl acetate extract. The structures were elucidated by spectroscopic methods. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.Article Citation - WoS: 14Citation - Scopus: 15Biotransformation of Ruscogenins by Cunninghamella Blakesleeana Nrrl 1369 and Neoruscogenin by Endophytic Fungus Neosartorya Hiratsukae(Elsevier Ltd., 2018) Özçınar, Özge; Tağ, Özgür; Yusufoğlu, Hasan; Kıvçak, Bijen; Bedir, ErdalBiotransformation of steroidal ruscogenins (neoruscogenin and ruscogenin) was carried out with Cunninghamella blakesleeana NRRL 1369 and endophytic fungus Neosartorya hiratsukae yielding mainly P450 monooxygenase products together with a glycosylated compound. Fermentation of ruscogenins (75:25, neoruscogenin-ruscogenin mixture) with C. blakesleeana yielded 8 previously undescribed hydroxylated compounds. Furthermore, microbial transformation of neoruscogenin by endophytic fungus N. hiratsukae afforded three previously undescribed neoruscogenin derivatives. While hydroxylation at C-7, C-12, C-14, C-21 with further oxidation at C-1 and C-7 were observed with C. blakesleeana, N. hiratsukae biotransformation provided C-7 and C-12 hydroxylated compounds along with C-12 oxidized and C-1(O) glycosylated derivatives. The structures of the metabolites were elucidated by 1-D (1H, 13C and DEPT135) and 2-D NMR (COSY, HMBC, HMQC, NOESY, ROESY) as well as HR-MS analyses.Article Citation - WoS: 27Citation - Scopus: 30Biotransformation of Cyclocanthogenol by the Endophytic Fungus Alternaria Eureka 1e1bl1(Elsevier Ltd., 2018) Ekiz, Güner; Duman, Seda; Bedir, ErdalThe microbial transformation of cyclocanthogenol (CCG), Astragalus sp. originated sapogenin, by the endophytic fungus Alternaria eureka 1E1BL1 isolated from Astragalus angustifolius was investigated. Hydroxylation, oxidation, epoxidation, O-methylation, ring-expansion and methyl migration reactions were observed on the triterpenoid skeleton. As a result, eight metabolites were isolated and the structures of the previously undescribed compounds were established by 1-D, 2-D NMR and HR-MS analyses.Article Citation - WoS: 19Citation - Scopus: 20Specialized Metabolites From the Aerial Parts of Centaurea Polyclada Dc.(Elsevier Ltd., 2017) Demir, Serdar; Karaalp, Canan; Bedir, ErdalThe genus Centaurea L. (Asteraceae) is represented by 200 taxa in the flora of Turkey and several Centaurea species are used as herbal remedies against different conditions. Previous phytochemical investigations on this genus generally revealed the isolation of sesquiterpene lactones and flavonoid derivatives. In our continuous search on Centaurea genus, a phytochemical study was performed on Centaurea polyclada DC., an endemic of West Anatolia. Previously undescribed two sesquiterpene-amino acid conjugates, an elemane and an eudesmane derivative were isolated from the aerial parts of Centaurea polyclada, together with eight known compounds; two elemane derivatives, three flavonoids, a lignan, a phenolic glucoside and a phenylpropanoid glucoside. Structural elucidation of the compounds was based on spectroscopic evidence, including 1D and 2D NMR and high-resolution mass spectrometry, chemical degradation results and reference data comparison. Sesquiterpene-amino acid conjugates are representatives of an unusual group of sesquiterpenes, and elemane-amino acid conjugates are herein reported for the first time in nature.