Sürdürülebilir Kalkınma Amaçları

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• MakaleYalnız künye2026Scopus SJRQ1/r/bayburt/11497
  Structure-guided discovery of submicromolar 1,2,4-triazole–Schiff-base inhibitors of glutathione reductase

  Manap, Sevda; Akar, Hande; Medetalibeyoğlu, Hilal; Atalay, Abdurrahman; Can, Zehra; Kara, Yakup; Alkan, Muzaffer; Beytur, Murat; Yüksek, Haydar; Ortaakarsu, Ahmet Buğra

  Glutathione reductase (GR) plays a crucial role in maintaining cellular redox balance and is a promising target for ferroptosis-based cancer therapies. In this study, we report the design, synthesis, and comprehensive evaluation of a novel series of 1,2,4-triazole–Schiff base succinate derivatives (AUR-514–518) as potent GR inhibitors. In vitro Mannervik assays revealed vigorous submicromolar inhibitory activity, with AUR-517 emerging as the most effective (IC50 = 0.471 ± 0.032 μM), significantly surpassing quercetin (IC50 = 214.5 ± 18.5 μM). Antioxidant profiling revealed negligible radical scavenging activity; however, modest CUPRAC responses suggest a target-specific mechanism. To elucidate the molecular determinants of inhibition, we employed deep-learning–assisted protein–ligand affinity predictions, molecular dynamics simulations, MM/GBSA free-energy calculations, and dimensional reduction analyses. These computational studies revealed dual binding modes at both the catalytic site and dimer interface, with AUR-517 forming stable interactions with key catalytic residues, consistent with experimental potency rankings. The RMSD/RMSF profiles indicated enhanced conformational stability of GR–ligand complexes, while binding energy landscapes underscored the superior stability of AUR-517. Consequently, these findings establish the AUR series as a new class of structurally validated GR inhibitors, with AUR-517 representing a lead scaffold for the rational development of ferroptosis-sensitizing agents with translational potential in oncology.

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  AtıfScopus3·WoS3·OpenAlex5

  İncele
• MakaleAçık Erişim2025Scopus SJRQ1/r/bayburt/11454
  Physicochemical characterization of glucan AK7 produced by quinoa sourdough isolate Leuconostoc mesenteroides AK7

  İspirli, Hümeyra; Arslan, Şeyma; Tuncer, Fatma; Kasapoglu, Muhammed Z.; Ortakcı, Fatih; Tuncil, Yunus Emre; Dertli, Enes

  The production of exopolysaccharides (EPS) by Lactic Acid Bacteria (LAB) is technologically crucial because it has a wide range of applications in food technology, biotechnology, and health. In the present work, a new quinoa sourdough isolate of Leuconostoc mesenteroides strain AK7 was identified as a novel producer of a dextran-type EPS. The monomeric units of EPS AK7 were confirmed by HPLC analysis, while NMR spectroscopy and GC–MS linkage analysis further verified the EPS structure as a branched dextran containing mainly (1 → 6)-linked α- D -glucose units with (1 → 3,6)-linked α- D -glucose unit as branching points. An average molecular weight of 1.2 × 106 Da was detected for glucan AK7. FTIR analysis was applied to determine the functional units of dextran AK7. In terms of thermal features, TGA and DSC analysis were applied and a specific degradation temperature of 300 °C was found for dextran AK7. The morphology of the lyophilized EPS displayed a rough, dense, and porous structure, as observed through SEM analysis. Dextran AK7 revealed a semi-crystalline nature detected by XRD analysis. These structural and functional properties of dextran AK7 produced by Leuconostoc mesenteroides AK7 from quinoa sourdough suggest its potential usage for food industry applications.

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  AtıfScopus3·WoS3·OpenAlex3

  İncele
• MakaleAçık Erişim2024Scopus SJRQ1/r/bayburt/13022
  Physicochemical and structural characterisation of a branched dextran type exopolysaccharide (EPS) from Weissella confusa S6 isolated from fermented sausage (Sucuk)

  Özpınar, Fatma Beyza; İspirli, Hümeyra; Kayacan, Selma; Korkmaz, Kader; Dere, Sevda; Sagdic, Osman; Alkay, Zuhal; Tunçil, Yunus Emre; Ayyash, Mutamed; Dertli, Enes

  Exopolysaccharide (EPS) producing Lactic Acid Bacteria (LAB) species can be presented in distinct environments. In this study, Turkish fermented sausage (sucuk) was tested for the presence of EPS producer LAB strains and slimy-mucoid colonies were selected for further tests. Among the isolates, Weissella confusa strain S6 was identified and tested for the physicochemical characterisation of its EPS. This strain was found to produce 0.74 g L−1 of EPS in modified BHI medium conditions. Structural characterisation of EPS S6 by 1H and 13C NMR demonstrated that EPS S6 was a highly branched dextran type glucan formed by mainly (1 → 2)-linked α-D-glucose units together with low levels of (1 → 3)-linked α-D-glucose units as branching points. This structure was further confirmed by methylation analysis detected by GC–MS. An average molecular weight of 8 × 106 Da was detected for dextran S6. The FTIR analysis supported the dextran structure and revealed the presence of distinct functional groups within dextran S6 structure. A strong thermal profile was observed for dextran S6 detected by DSC and TGA analysis and dextran S6 revealed a degradation temperature of 289 °C. In terms of physical status, dextran S6 showed amorphous nature detected by XRD analysis. SEM analysis of dextran S6 demonstrated its rough, compact and porous morphology whereas AFM analysis of dextran S6 detected in its water solution showed the irregularity with no clear cross-link within the dextran chains. These technological features of dextran S6 suggests its potential to be used for in situ or ex situ application during meat fermentations.

  AtıfScopus25·WoS24·OpenAlex29

  İncele
• MakaleAçık Erişim2024Scopus SJRQ1/r/bayburt/12896
  Synthesis of flaxseed gum/melanin-based scaffold: A novel approach for nano-encapsulation of doxorubicin with enhanced anticancer activity

  Kumar, Deepak; Pal, Ravi Raj; Das, Neeladri; Roy, Partha; Saraf, Shubhini A.; Bayram, Sinan; Kundu, Patit P.

  Doxorubicin is a powerful chemotherapy medicine that is frequently used to treat cancer, but because of its extremely destructive side effects on other healthy cells, its applications have been severely constrained. With the aim of using lower therapeutic doses of doxorubicin while maintaining the same anti-cancerous activity as those of higher doses, the present study designs nano-encapsulation of doxorubicin by acrylamide grafted melanin as core and acrylic acid grafted flax seed gum as shell (DOX@AAM-g-ML/AA-g-FSG-NPs) for studies in-vivo and in-vitro anticancer activity. For biological studies, the cytotoxicity of DOX@AAM-g-ML/AA-g-FSG-NPs was examined on a cancerous human cell line (HCT-15) and it was observed that DOX@AAM-g-ML/AA-g-FSG-NPs exhibited very high toxicity towards HCT-15. In-vivo investigation in colon cancer-inflicted rat model also showed that DOX@AAM-g-ML/AA-g-FSG-NPs showed better anticancer activity against cancerous cells as compared to free doxorubicin. The drug release behavior of DOX@GML-GFS-NPs was studied at several pH and maximum drug release (95 %) was recorded at pH -7.2, and kinetic data of drug release was follows the Higuchi (R2 = 0.9706) kinetic model. Our study is focussed on reducing the side effects of doxorubicin by its nano-encapsulation in acrylamide grafted melanin as core and acrylic acid grafted flax seed gum that will also enhance its efficiency.

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  AtıfScopus14·WoS14·OpenAlex15

  İncele
• MakaleAçık Erişim2023Scopus SJRQ1/r/bayburt/11610
  Structural characterization of potato starch modified by a 4,6-α-glucanotransferase B from Lactobacillus reuteri E81

  Hassanein, Wael S.; İspirli, Hümeyra; Dertli, Enes; Yilmaz, Mustafa Tahsin

  The recent reports have revealed that increase in amount of α-1,6 linkages by modification of potato starch with enzyme (glycosyltransferases) treatment gains slowly digestible properties to the starch; however, the formation of new α-1,6-glycosidic linkages diminish the thermal resistance of the starch granules. In this study, a putative GtfB-E81, (a 4,6-α-glucanotransferase-4,6-αGT) from L. reuteri E81 was firstly used to produce a short length of α-1,6 linkages. NMR results revealed that external short chains mostly comprised of 1–6 glucosyl units were newly produced in potato starch, and the α-1,6 linkage ratio was significantly increased from 2.9 % to 36.8 %, suggesting that this novel GtfB-E81 might have potentially an efficient transferase activity. In our study, native and GtfB-E81 modified starches showed fundamental similarities with respect to their molecular properties and treatment of native potato starch with GtfB-E81 did not remarkably change thermal stability of the potato starch, which seems to be very prominent for the food industry given the significantly decreased thermal stability results obtained for the enzyme modified starches reported in the literature. Therefore, the results of this study should open up emerging perspectives for regulating slowly digestible characteristics of potato starch in future studies without a significant change in the molecular, thermal, and crystallographic properties.

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  AtıfScopus14·WoS14·OpenAlex18

  İncele
• MakaleYalnız künye2023Scopus SJRQ1/r/bayburt/11601
  Utilisation of an active branching sucrase from Lactobacillus kunkeei AP-37 to produce techno-functional poly-oligosaccharides

  İspirli, Hümeyra; Korkmaz, Kader; Arioglu-Tuncil, Seda; Bozkurt, Fatih; Sağdıç, Osman; Tunçil, Yunus Emre; Narbad, Arjan; Dertli, Enes

  Glucansucrase AP-37 was extracted from the culture supernatant of Lactobacillus kunkeei AP-37 and characteristics of the glucan produced by the active glucansucrase in terms of structural and functional roles were determined in this study. A molecular weight around 300 kDa was observed for glucansucrase AP-37 and its acceptor reactions with maltose, melibiose and mannose were also conducted to unveil the prebiotic potential of the poly-oligosaccharides formed via these reactions. The core structure of glucan AP-37 was determined by 1H and 13C NMR and GC/MS analysis which revealed that glucan AP-37 was a highly branched dextran composing of high levels of (1 → 3)-linked α-D-glucose units with low levels of (1 → 2)-linked α-D-glucose units. The structural features of the glucan formed, demonstrated that glucansucrase AP-37 was an α-(1 → 3) branching sucrase. Dextran AP-37 was further characterised by FTIR analysis and XRD analysis demonstrated its amorphous nature. A fibrous compact morphology was observed for dextran AP-37 with SEM analysis whereas TGA and DSC analysis revealed its high stability as no degradation was observed up to 312 °C. Finally, the prebiotic potential of the dextran AP-37 and the gluco-oligosaccharides produced with the acceptor reaction of α-(1 → 3) branching sucrase AP-37 were determined and promising results were found for the gluco-oligosaccharides to act as prebiotics.

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  AtıfScopus13·WoS12·OpenAlex13

  İncele
• MakaleYalnız künye2022Scopus SJRQ1/r/bayburt/12036
  Structural and bioactive characteristics of a dextran produced by Lactobacillus kunkeei AK1

  Yilmaz, Mustafa Tahsin; İspirli, Hümeyra; Taylan, Osman; Bilgrami, Anwar L.; Dertli, Enes

  In this study, structural and techno-functional characteristics of an exopolysaccharide (EPS) produced by Lactobacillus kunkeei AK1 were determined. High-performance liquid chromatography (HPLC) analysis demonstrated that EPS AK1 was composed of only glucose units. 1H and 13C Nuclear magnetic resonance (NMR) analysis revealed that EPS AK1 was a dextran type EPS containing 4.78% (1 → 4)-linked α-D-glucose branches. The molecular weight of EPS AK1 was determined to be 45 kDa by Gel Permeation Chromatography (GPC) analysis. A high level of thermal stability up to 280 °C was determined for dextran AK1 detected by Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA). Dextran AK1 appeared as regular spheres with compact morphology and as irregular particles in the solution with no clear cross-linking between the chains of the polysaccharide observed by Scanning electron microscopy (SEM) and Atomic force microscopy (AFM) analysis, respectively. X-ray diffraction analysis (XRD) analysis demonstrated that dextran AK1 had a crystalline structure. A relatively strong antioxidant activity was observed for dextran AK1 determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging and cupric reducing antioxidant capacity (CUPRAC) tests. Finally, only a digestion ratio of 3.1% was observed for dextran AK1 following the in vitro simulated gastric digestion test.

  AtıfScopus43·WoS39·OpenAlex41

  İncele
• MakaleYalnız künye2020Scopus SJRQ1/r/bayburt/13583
  Structural and physicochemical characterisation and antioxidant activity of an α-D-glucan produced by sourdough isolate Weissella cibaria MED17

  Aburas, Hani; İspirli, Hümeyra; Taylan, Osman; Yilmaz, Mustafa Tahsin; Dertli, Enes

  An exopolysaccharide (EPS) producer slimy-mucoid type colony was isolated from sourdough and identified as Weissella cibaria MED17. The 1H and 13C NMR spectra of EPS MED17 demonstrated that this EPS was a dextran type glucan ((1 → 6)-linked α-D-glucose core structure) containing (1 → 3)-linked α-D-glucose branches and proportion of (1 → 6)-linked α-D-glucose units to (1 → 3)-linked α-D-glucose units was 94.3:5.7%. The FTIR analysis also confirmed the (1 → 6)-linked α-D-glucose linkage. A high level of thermal stability was observed for glucan MED17 as no degradation up to 300 °C was observed by TGA and DSC analysis. The XRD analysis of glucan MED17 showed its semi- crystalline nature and its compact sheet-like morphology was observed by SEM analysis. Finally, antioxidant characteristics of glucan MED17 were determined by ABTS and DPPH radical scavenging activity tests that revealed a moderate antioxidant activity of glucan MED17. These findings show potential techno-functional characteristics of glucan MED17.

  AtıfScopus58·WoS55·OpenAlex59

  İncele
• MakaleAçık Erişim2019Scopus SJRQ1/r/bayburt/13918
  Characterization of a 4,6‑α‑glucanotransferase from Lactobacillus reuteri E81 and production of malto-oligosaccharides with immune-modulatory roles

  İspirli, Hümeyra; Şimşek, Ömer; Skory, Christopher; Sağdıç, Osman; Dertli, Enes

  A wide number of Lactic Acid Bacteria (LAB) species produce α-glucans with their ability to synthesize glucansucrases (GS) which use sucrose as substrate for the glucan production. Recently another group of enzymes in LAB gained special interest for their ability to produce α-glucans targeting the substrates containing α1-4-linkages and synthesizing new (α1-6) or (α1-3)–linkages as α‑glucanotransferases. In this study, a putative 4,6‑α‑glucanotransferase (GTFB) from sourdough isolate Lactobacillus reuteri E81 was identified and expressed in Escherichia coli. The biochemical characterization of the GTFB-E81 confirmed its function as it cleaved the α1-4-linkages in different substrates and produced new gluco-oligomers/polymers containing α1-6 linkages together with the α1-4-linkages detected by NMR analysis. GTFB-E81 produced malto-oligosaccharides targeting maltose and maltoheptaose as substrates with up to DP 8 detected by TLC and ESI-MS/MS analysis. The functional roles of these malto-oligosaccharides were determined by testing their immune-modulatory functions in HT29 cells and they triggered the production of anti-inflammatory 1L-4 and pro-inflammatory IL-12 cytokines.

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  AtıfScopus43·WoS40·OpenAlex42

  İncele
• MakaleYalnız künye2019Scopus SJRQ1/r/bayburt/13352
  Partial characterization of a levan type exopolysaccharide (EPS) produced by Leuconostoc mesenteroides showing immunostimulatory and antioxidant activities

  Taylan, Osman; Yilmaz, Mustafa Tahsin; Dertli, Enes

  Leuconostoc mesenteroides S81 was isolated from traditional sourdough as an exopolysaccharide (EPS) producer strain. The monosaccharide composition of the EPS from strain S81 was characterized by HPLC analysis and only fructose was found in the repeating unit structure. The NMR spectroscopy analysis revealed that EPS was a levan type EPS as a β-(2 → 6)-linked fructan. The FTIR analysis further confirmed the presence of the furanoid rings in the EPS structure. The levan S81 showed high level of thermal stability determined by DSC and TGA analysis. The lyophilised levan S81 showed a sheet-like compact morphology and its aqueous solution formed spheroidal lumps with a compact structure detected by SEM and AFM analysis, respectively. Importantly the levan S81 showed a high level of immunomodulatory role, induced the anti-inflammatory cytokine IL-4, and exhibited a strong antioxidant capacity with EC50 value 1.7 mg mL−1 obtained by hydroxyl radical scavenging activity test under in vitro conditions. These findings reveal potential of levan S81 for technological purposes and as a potential natural immunomodulatory and antioxidant.

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  AtıfScopus132·WoS112·OpenAlex126

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