Araştırmacılar(9)

• Akman, Tugrul Cagri
• Akşit, Hüseyin
• Aydemir, Emircan
• Erken, İrem Nisa
• Gergin, Ömer
• Taşkor Önel, Gülce
• Türkmenoğlu, Burçin
• Yıldırım, Sümeyra Tuna
• Yilmaz, Mustafa Abdullah

• ArticleYayıncıda açık erişim2027/r/ebyu/10362
  From extraction to ocular delivery: An integrated approach using apigenin and apigenin 7-O-glucoside nanosuspensions to treat corneal neovascularization

  Aytekin, Eren; Gözcü, Sefa; Polat, Heybet Kerem; Akşit, Hüseyin; Karakuyu, Nasıf Fatih; Kurt, Nihat; Sofu, Gülşah Usta; Akkaya, Züleyha Yalnız; Tebrizi, Behzat; Çalış, Sema

  Corneal neovascularization (CV) is a vision-threatening condition characterized by the pathological ingrowth of blood vessels. While corticosteroids and anti-VEGF agents are standard treatments, their prolonged use is associated with significant ocular side effects. This study aimed to develop and optimize nanosuspensions of Apigenin (APG) and Apigenin-7-O-glucoside (APG 7) to enhance their ocular bioavailability and evaluate their efficacy in the treatment of CV. APG and APG 7 were isolated from Petroselinum crispum . Nanosuspensions were formulated using an anti-solvent precipitation method, optimized via a 23 factorial design considering PVA concentration, Span 80 concentration, and homogenization speed. The physical properties, including particle size, PDI, and zeta potential, were characterized. In vivo efficacy was assessed over a 7-day treatment period in an alkali-burn induced rat CV model through clinical scoring, histopathology, and immunohistochemical analysis of VEGFA and IL-6 expression. The optimized APG nanosuspensions exhibited a mean particle size of ∼166.9 nm with high stability. In vivo studies demonstrated that 0.05% APG nanosuspension significantly inhibited corneal angiogenesis, reduced stromal edema, and downregulated VEGFA and IL-6 expression compared to the untreated injury group (p < 0.05). Conversely, APG 7 formulations failed to show significant therapeutic efficacy, likely due to limited corneal permeability attributed to the glycoside moiety. The 0.05% APG nanosuspension presents a promising, non-invasive therapeutic alternative for CV management, offering effective anti-angiogenic activity with improved ocular delivery characteristics.

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• ArticleYalnız künye2027/r/ebyu/10289
  Synthesis, structural characterization, and in vitro and in silico anticancer evaluation of chalcone-based heterocyclic and boron difluoride derivatives

  Serdaroğlu, Vildan; Demir, Fatma; Aydın, Ali; Türkmenoğlu, Burçin; Kahriman, Nuran

  In this research, a series of novel bioactive heterocyclic polar compounds were designed and synthesized by incorporating various functional groups to enhance their biological and functional properties. The work involved the synthesis of chalcone (1–9, 10–18), boron difluoride complex (19–21), pyrazoline (22–25), and pyrimidine (26–37) compounds with their structures characterized through spectral techniques including NMR (1H, 13C (APT), 1H–1H COSY), FT-IR spectroscopies, LC-MS spectrometry. The anticancer potential of all compounds was assessed using lung cancer cell lines (A549, Calu1, H1650), brain cancer cell lines (A172, C6, B35), as well as normal lung (Beas2B) and chondrocyte (HC) cell lines. Compounds exhibiting a GI50 value below 3.0 µg/mL and a TGI value under 100 µg/mL were classified as having anticancer activity, based on comparisons with the reference drug 5-fluorouracil (5FU). Overall, compounds 24, 34, and 36 emerged as the most promising lead candidates by combining potent antiproliferative activity, favorable GI50-derived selectivity indices, and low toxicity toward normal cells, whereas compounds 2, 32, and 35 demonstrated the highest overall biological potency across multiple cancer cell lines. Representative GI50 values as low as 1.0–1.2 µg/mL, TGI values as low as 1.3–2.5 µg/mL, and LC50 values generally exceeding 500 µg/mL in normal cell lines were obtained in the most responsive models, supporting the potential of these derivatives for further anticancer development. To support these detailed in vitro studies, the most active compounds targeting TP53, EGFR, Akt1, mTOR, ERK2, and caspase 3, which are effective in lung and brain cancer pathways, were interacted via in silico molecular docking. Through molecular docking, the interaction values of compounds 2, 6, 7, 8, 13, 14, 17, 18, 24, 27, 32, 35, 36, and 37 with the determined targets were calculated, and their potential as promising lead candidates for drug development was analyzed.

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• ArticleYayıncıda açık erişim2026/r/ebyu/11458
  Phytochemical profiling of Artemisia absinthium essential oils from different regions of Türkiye and preliminary evaluation of their antibacterial and honeybee locomotor effects

  PORTAKAL, Pınar; TUFEKCI, Ali Rıza; ARSLAN, Okan Can; AKŞIT, Hüseyin; GÖÇERI, Ali; KÜRSAT, Murat

  This study aimed to determine the phytochemical composition of essential oils obtained from Artemisia absinthium collected in Sivas (AAS), Erzincan (AAE) and Hakkari (AAH) and to evaluate their effects on honeybee locomotor activity. The chemical composition of the essential oils was analyzed by GC–MS, revealing notable regional differences. Chamazulene was identified as the predominant compound in all samples, with the highest concentration in AAH (64.6%), while AAE was characterized by a high β-thujone content (18.3%). Locomotor activity assays showed no significant differences between control and treated groups over a 24-hour period (H (3) = 4.270, p=0.234; F (3,121)=0.867, p=0.460), indicating no detectable acute locomotor alterations under the tested conditions. The antibacterial activity of the essential oils was evaluated using the disc diffusion method against both Gram-positive and Gram-negative bacteria. Antibacterial effects varied depending on the oils' geographical origin and chemical composition. AAE and AAS essential oils showed comparatively larger inhibition zones, particularly against Staphylococcus aureus and Bacillus cereus, whereas AAH showed selective activity against Pseudomonas aeruginosa. No inhibition of Listeria monocytogenes was observed with any of the tested oils. Overall, the oils' antibacterial activity was moderate and selective compared with the positive control, imipenem. These findings suggest that regional variation significantly influences the chemical composition and biological activity of A. absinthium essential oils. Furthermore, the tested oils did not produce detectable acute locomotor alterations in honeybees under the conditions tested. These findings provide preliminary insight into the relationship between regional phytochemical variability and the biological properties of A. absinthium essential oils.

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• ArticleYalnız künye2026/r/ebyu/11095
  Chemical Composition and Antibacterial Activity of Rosa villosa subsp. mollis R. Keller & Gams., Rosa hemisphaerica J. Herrm. and Natural Hybrid Rosa ozcelikii Korkmaz & Kandemir Essential Oil

  Gözcü, Sefa; Akşit, Zeynep; Akşit, Hüseyin; Şimşek, Samed; Korkmaz, Mustafa

  This study explores the essential oils (EOs) of Rosa hemisphaerica (RH), Rosa villosa subsp. mollis (RV) and the newly identified hybrid Rosa ozcelikii (RO). The major components of the EOs were found to be nonadecane (22.45%), viridiflorol (19.37%) and heneicosane (11.72%) in RH; α-muurolene (14.72%), σ-cadinene (17.88%) and farnesol (9.94%) in RV; and heptacosane (27.63%), heneicosane (12.42%) and α-citronellol (11.90%) in RO. Antibacterial activities were evaluated using the disc diffusion method. The EOs demonstrated moderate antibacterial effects: RV and RH exhibited inhibition zones of 8.0 ± 0.4 mm against Pseudomonas aeruginosa, while RO showed stronger activity with inhibition zones of 11.0 ± 0.5 mm against Staphylococcus aureus, 12.0 ± 0.4 mm against Clostridium perfringens and 9.0 ± 0.5 mm against Bacillus cereus. These findings highlight the chemical diversity and potential therapeutic applications of these Rosa species, emphasising their relevance in the search for natural antimicrobial agents.

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• ArticleYalnız künye2026/r/ebyu/11024
  Novel Imino Derivatives of Thymol: Synthesis, in vitro Cytotoxic Activities, Molecular Docking Analysis and ADME Prediction

  Başaran, Eyüp; Türkmenoğlu, Burçin; Akkoc, Senem

  Cancer is a significant global health challenge that affects millions of individuals every year. The development of new anticancer drugs is imperative to address the issue of drug resistance in cancer therapy. Therefore, in this study, novel imino derivatives of thymol (3a-c) were synthesized and evaluated as anticancer agents. These compounds were structurally elucidated using elemental analysis and various spectroscopic methods, including 1H and 13C Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FT-IR). The cytotoxic activities of the new compounds on human liver cancer (HepG2) and healthy human kidney (HEK-293T) cell lines were investigated. Compounds were tested at various concentrations to determine their IC50 values. Among the tested new compounds, 3a and 3b demonstrated cytotoxicity in HepG2, with IC50 values of 88.97 µM and 106.10 µM, respectively. Furthermore, compound 3a also exhibited significant toxicity against the HEK-293T cell line, suggesting that further modifications are needed to improve selectivity for healthy cells. ADME properties analysis resulted in the detection of two lead compounds (3a and 3b) among compounds 2a-c and 3a-c. For the most active compounds 3a and 3b, molecular docking study on epidermal growth factor tyrosine kinase receptor (PDB ID: 3POZ), PI3K alpha (PDB ID: 4FA6), c-kit tyrosine kinase (PDB ID:1T46) was performed to verify the in vitro experimental results.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10931
  Design and biological evaluation of sulfonamide–chalcone hybrids with in vitro tumor-selective cytotoxicity against oral squamous cell carcinoma: SAR, QSAR, and in silico ADME studies

  Ozli, Gulsen; Sakagami, Hiroshi; Polat, M. Fatih; Kazaz, Cavit; Kurosaki, Kota; Uesawa, Yoshihiro; Inden, Kaito; Gul, Halise Inci

  Multidrug resistance and off-target toxicity remain major challenges in the treatment of oral squamous cell carcinoma (OSCC). In this study, sulfonamide-chalcone hybrids were designed by combining the chalcone scaffold with a benzenesulfonamide moiety to explore tumor-selective cytotoxicity and structure-activity relationships. Thirty-two N-(4-(3-(aryl)prop-2-enoyl)phenyl)benzenesulfonamide derivatives, including 17 previously unreported compounds, were synthesized via base-catalyzed Claisen-Schmidt condensation and characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Cytotoxicity was evaluated against the human OSCC cell lines Ca9-22 and HSC-2 and non-malignant human gingival fibroblasts and human pulp cells. Compounds 5, 13, 21, 30, and 32 showed the most favorable activity/selectivity profiles, with 50% cytotoxic concentration values of 1.6–2.2 µM against Ca9-22 cells and tumor-selectivity index values of 14.6–21.1. Structure-activity relationship analysis indicated that meta- and para-substitution patterns generally favored tumor-selective cytotoxicity, whereas bulky ortho-substituents reduced activity. Descriptor-based quantitative structure-activity relationship analysis suggested associations between cytotoxicity and molecular shape, polarizability, electronic properties, polarity, and surface descriptors. In silico studies indicated variable gastrointestinal absorption among the selected lead compounds, while none were predicted to permeate the blood–brain barrier. The selected leads also complied with Lipinski’s Rule of Five. Overall, these findings suggest that sulfonamide–chalcone hybrids represent potentially useful tumor-selective cytotoxic scaffolds for further OSCC-focused optimization. (Figure presented.)

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• ArticleYalnız künye2026/r/ebyu/10927
  Design, synthesis, and computational studies of pyridine-substituted 1,2,3-triazoles with anticancer and antibacterial activities

  Dilitatlı, Sümeyye; Demirbanka, Fatma Gül Özçelik; Türkmenoğlu, Burçin; Köse, Muhammet

  A new series of pyridine-based 1,2,3-triazole derivatives (SD5–7) was synthesized through Cu(I)-catalyzed azide–alkyne cycloaddition and fully characterized by FT-IR, NMR, HRMS, and elemental analysis. The molecular structures of SD6 and SD7 were further confirmed by single-crystal X-ray diffraction, which revealed stabilizing π–π stacking and weak intermolecular interactions. Additionally, the properties of compounds SD5, SD6, and SD7 were investigated by density functional theory using B3LYP/6-311G*. Cytotoxic properties were investigated against OUMS (cancerous) and HUVEC (healthy) cell lines using MTS assays. SD5 exhibited the most potent effect on OUMS cells (IC50 = 98.05 µg/mL), exceeding the activity of cisplatin, while SD6 displayed statistically significant selectivity between cancer and normal cells. Antibacterial screening against Gram-positive (S. aureus, B. cereus) and Gram-negative (E. coli, K. pneumoniae) strains showed that SD5 and SD6 had moderate inhibitory effects (MIC = 5 mg/mL), whereas SD7 was inactive. These results suggest that pyridine-substituted 1,2,3-triazoles represent valuable scaffolds with promising dual anticancer and antibacterial potential for further development. Compounds SD5–7 exhibited cytotoxic effects against the OUMS cell line within the concentration range of 98.05–876.0 µg/mL, while in antibacterial tests, the ligands showed lower activity compared to streptomycin. SD5 and SD6 compounds, whose activity was determined in vitro studies, were analyzed to elucidate the interaction mechanism with the targets identified in molecular docking studies. Compounds SD5 and SD6 were analyzed in molecular docking studies by interacting with the crystal structures of 5I96 and 6U4J.

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• ArticleYalnız künye2026/r/ebyu/10876
  Synthesis and characterization of 2,3-diaminophenazine@CuhNFs and 2,3-diaminopyridine@CuhNFs: a new strategy to enhance anticancer activity

  Somturk-Yilmaz, Burcu; Turkmenoglu, Burçin; Akkoc, Senem

  In this study, synthesis and characterization of 2,3-diaminophenazine@CuhNFs and 2,3-diaminopyridine@CuhNFs were carried out. The morphologies of the synthesized CuhNFs were investigated using Fourier Transform Infrared spectrometry, scanning electron microscopy and energy dispersive X-ray, elemental mapping, and XRD spectroscopy. Organic compounds and synthesized nanoflowers were screened against human lung (A549) and breast (MCF-7) cancer cell lines. The results show that the tested compounds had cytotoxic activity in both cell lines. To support the in vitro part of the study, the MTT results were also examined by in silico approaches. The binding parameter values of compounds interacting via in silico with 1M17 and 3ERT crystal structures in molecular docking and important amino acids in the binding site were determined. The pharmacokinetic properties and toxicity of compounds were evaluated using ADMET analysis.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10842
  Chemical Composition and Biological Activities of Propolis From Eastern Anatolia: Antioxidant, Enzyme Inhibitory, and Antimicrobial Activities

  Fırat, Mehmet Çağlar; Akşit, Zeynep; Şimşek, Samed; Altın, Sevgi; Yıldız, İlyas; Akşit, Hüseyin

  Propolis is recognized for its biological activities; however, its chemical composition varies according to environmental conditions, which presents challenges for quality standardization and biological evaluation. Although propolis has been widely investigated, information regarding variation among samples collected from geographically close locations within the same region is limited. Therefore, this study investigated whether propolis samples obtained from different locations within Erzincan Province exhibit differences in chemical composition and biological activities and evaluated the relationship between environmental conditions and propolis characteristics. Eleven propolis samples collected from Erzincan, Türkiye, were analyzed for phenolic composition, antioxidant capacity, antimicrobial activity, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase inhibitory activities. Twenty-eight compounds were identified, with gallic acid, protocatechuic acid, chlorogenic acid, hydroxybenzaldehyde, caffeic acid, and vanillin detected as major constituents. AChE inhibitory activity varied between 1.28 and 6.44 µg/mL, while BChE inhibitory activity varied between 1.85 and 9.66 µg/mL. All samples exhibited antibacterial activity. Total phenolic and flavonoid contents were 141.70–255.04 mg GAE/g extract and 30.48–93.81 mg QE/g extract, respectively. The KMH sample showed the antioxidant activity. The results demonstrated variation in phytochemical composition and biological activities among propolis samples collected within the same province, indicating associations between flora, environmental conditions, propolis quality, and bioactivity.

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• ArticleYalnız künye2026/r/ebyu/10831
  Ensuring pharmaceutical safety: Highthroughput LC-MS/MS method for plastic additive detection

  Demircioğlu, İbrahim Hakkı; Dalkılıç, Oğuzhan; Çelik, Saffet; Akman, Tugrul Cagri; Kılıç, Hamdullah; Kandemir, Levent; Atila, Alptuğ

  Extractables and Leachables studies require highly reliable and sensitive analytical methods to ensure pharmaceutical product safety. Plastic additives are widely used during production to improve the physicochemical properties of polymeric products. However, these additives may constitute a potential toxicological risk by contaminating active pharmaceutical ingredients and pharmaceutical preparations. In this study, a short-term, sensitive, accurate, and reliable LC-MS/MS method was developed for the analysis of 15 plastic additives defined in the European Pharmacopoeia and validated in accordance with the ICH Q2(R2) guideline. An electrospray ionization source was used for the analyses in both negative and positive modes. Chromatographic separation was carried out using a reverse-phase phenyl C18 column and a mixture of methanol and ultrapure water containing 5 mM ammonium acetate as the mobile phase by the gradient elution method. As a result of method optimization, the flow rate and total analysis time were determined to be 0.7 mL/min and 15 min, respectively. Diphenyl phthalate was chosen as the internal standard. The LLOQ values of plastic additives were generally determined as 50 ng/mL (150 ng/mL for oleamide). The reliability of the method was verified by intraday/interday precision and accuracy analyses. Both extractable and leachable studies were performed using the developed method. It was effectively used to detect plastic additive contamination in pharmaceutical products such as bromobutyl stoppers, LDPE containers, disposable eye drop packaging, and polypropylene bags. The developed LC-MS/MS method was successfully applied to the analysis of pharmaceutical formulations containing 1.4% polyvinyl alcohol and 0.6% povidone, sodium hyaluronate, salbutamol sulfate, and 0.9% isotonic sodium chloride.

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