İlgi alanları

• MakaleYalnız künye2026Scopus SJRQ2/r/bayburt/10743
  Novel heteroaromatic compounds bearing thiosemicarbazone as anti-cancer and anti-bacterial agents: Synthesis, cytotoxic and biological screening, molecular docking and DFT analysis

  Nartop, Dilek; Ögütcü, Hatice; Özkan, Elvan Hasanoglu; Yetim, Nurdan Kurnaz; Kizil, Hamit Emre; Ekincioglu, Yavuz

  Novel heteroaromatic compounds (Hc1, Hc2, Hc3, Hc4) were obtained, and their structure were confirmed using various spectroscopic methods, including elemental analysis, fourier transform infrared (FT-IR) spectroscopy, proton and carbon nuclear magnetic resonance (1H/13C-NMR) spectroscopy, and molar conductance measurement. The biological activities of the heteroaromatic compounds against several Gram-positive (Micrococcus luteus ATCC9341, Staphylococcus epidermidis ATCC12228, Bacillus cereus RSKK863, Listeria monocytogenes ATCC 19111), and Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC27853, Klebsiella pneumonia ATCC27853, Enterobacter aerogenes ATCC51342, Salmonella typhi H NCTC9018394, Shigella dysenteriae NCTC2966, Proteus vulgaris RSKK96026) were evaluated using the well-diffusion method. In general, the heteroaromatic compounds demonstrated a stronger inhibitory effect against Gram-positive bacteria. Hc1, Hc2 and Hc3 showed the highest inhibitory effect against B. cereus and L. monocytogenes. The compound (Hc4) showed the highest antibacterial activity and antifungal activity against Bacillus cereus and C. albicans, respectively. The cytotoxic activity of the heteroaromatic compounds was assessed against the non-small cell lung cancer cell line (NCI-H460) using the NutriCulture Cell Viability Detection Kit-8 (CVDK-8). Among the synthesized heteroaromatic compounds, Hc3 exhibited significant cytotoxic activity with an IC50 value of 141.3 & micro;g/mL, whereas compounds Hc1, Hc2, and Hc4 did not display significant toxicity at the tested concentrations. The molecular geometry of the heteroaromatic compound (Hc3) was optimized using Gaussian 09 W at the B3LYP/6-311++G (d,p) level of theory. Key structural parameters such as bond lengths, bond angles, and dihedral angles were determined through the same computational framework. Electronic features, including frontier molecular orbitals, global reactivity descriptors, and molecular electrostatic potential surfaces, were analyzed to explore intramolecular charge distribution and predict reactive sites. To evaluate the biological potential of the heteroaromatic compound (Hc3), molecular docking studies were performed. Additionally, drug-likeness assessment based on Lipinski's Rule of Five and ADME profiling revealed favorable pharmacokinetic characteristics. Molecular docking studies revealed that compound Hc3 showed a binding energy of -4.09 kcal/mol against the EGFR target (PDB ID: 1UWH), exhibiting key interactions such as hydrogen bonding and It-interactions with the active site residues. Based on all the results, it can be said that new heteroaromatic compounds have significant potential in the pharmaceutical field.

  AtıfScopus1

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• MakaleYayıncıda açık erişim2026/r/bayburt/12794
  A natural nephroprotective adjuvant for cancer chemotherapy: Rosmarinic acid disrupts IL-17 A-Ferroptosis coupling in Ifosfamide-induced renal injury

  Süzen Celbek, Büşra; Şimşek, Hasan; Akaras, Nurhan; Kandemir, Özge; Kızıl, Hamit Emre; Mutlu, Hüseyin; Kandemir, Fatih Mehmet

  Rosmarinic acid (RA) is a natural polyphenol with established pleiotropic protective effects. Ifosfamide (IFA) is a potent antineoplastic agent whose clinical utility is severely limited by dose-dependent nephrotoxicity, primarily mediated by its metabolite, chloroacetaldehyde (CAA). This study aimed to investigate whether RA protects against IFA-induced nephrotoxicity and to elucidate the underlying molecular mechanisms. Male Wistar albino rats (n = 7 per group) were allocated into four groups: Control, RA-only (50 mg/kg, p.o., 2 days), IFA-only (a single 500 mg/kg, i.p. dose), and IFA + RA. Serum biochemical markers (urea, creatinine), renal oxidative stress parameters (MDA, GSH, SOD, CAT, GPx), gene expression levels (NF-κB, TNF-α, IL-1β, IL-17 A, ACT1, TRAF6, Caspase-3, Bax, Bcl-2, PTGS2, GPX4, TfR1), and histopathological/immunohistochemical analyses (KIM-1, Nephrin, Caspase-3) were performed 24 h post-administration. IFA induced severe renal dysfunction, marked oxidative stress, and extensive histopathological damage. Mechanistically, IFA initiated a pathogenic cascade activating intrinsic apoptosis and ferroptosis, driven by a self-sustaining IL-17 A-TRAF6-NF-κB inflammatory loop. RA co-treatment (50 mg/kg) significantly reversed all functional, biochemical, and histological damage by strategically breaking this crosstalk, restoring redox homeostasis, and simultaneously restraining both cell death programs. In conclusion, RA protects against IFA nephrotoxicity by targeting the critical inflammation-ferroptosis coupling, positioning it as a highly promising adjuvant candidate for clinical use to mitigate IFA-induced renal injury.

  AtıfScopus3·WoS4

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• MakaleYalnız künye2026/r/bayburt/11344
  Synthesis and cytotoxic activity studies of novel heterocyclic thiosemicarbazone compounds as anticancer agents

  Güllü, Eda; Hasanoğlu Özkan, Elvan; Kızıl, Hamit Emre; Nartop, Dilek

  Herein, novel heterocyclic thiosemicarbazone compounds (Hb1, Hb2, Hb3) containing pyrimidine, imidazole, pyridine, and phenyl rings were synthesized via the condensation method as potential therapeutic agents for the treatment of non-small cell lung cancer. The structure of novel heterocyclic compounds was elucidated by using some spectroscopic techniques (organic elemental analysis, fourier transform infrared spectroscopy, proton/carbon nuclear magnetic resonance spectroscopy, scanning electron microscopy and energy dispersive X-ray image, and molar conductance measurement). The antiproliferative activity of novel heterocyclic thiosemicarbazone compounds using CVDK-8 cell viability assay. The viability assay was examined against A549 human non-small cell lung cancer cell line. All heterocyclic thiosemicarbazone compounds exhibited varying degrees of dose-dependent cytotoxic activity against A549 NSCLC cells. The results showed that the pyridine-based heterocyclic compound (Hb3) was the most potent antiproliferative agent, demonstrating a dose-dependent reduction in cell viability at concentrations of 50 µg/mL and higher.

  İncele
• MakaleYayıncıda açık erişim2026/r/bayburt/11260
  Synthesis and pharmacokinetic profiling of a novel pyrimidine imidazole based thiosemicarbazone derivative for BRAF inhibition in lung cancer therapy

  Ekincioğlu, Yavuz; Kızıl, Hamit Emre; Güllü, Eda; Özkan, Elvan Hasanoğlu; Nartop, Dilek

  This study presents the design, synthesis, and comprehensive evaluation of a novel thiosemicarbazone derivative containing a pyrimidine-imidazole (C11H11N8SCl) as a potential BRAF inhibitor for the treatment of non-small cell lung cancer. The compound was synthesized by a condensation reaction and characterized by elemental analysis, molar conductivity, SEM-EDS, FT-IR, 1H, and 13C-NMR spectral techniques. DFT calculations at the B3LYP/6-311 + + G(d, p) level revealed a HOMO-LUMO gap of 2.8 eV, indicating appropriate molecular stability and reactivity. Molecular docking studies with BRAF (PDB ID: 1UWH) demonstrated favorable binding affinity (-6.85 kcal/mol) with key interactions at ILE512, HIS509, HIS584, GLN529, GLU585, LYS590, VAL510, and LEU587 residues. In vitro cytotoxicity assays revealed that the compound possesses anticancer potential against H-460 cells, with a significant inhibitory effect observed at a concentration of 200 µg/mL. Combined with its favorable binding affinity toward BRAF kinase, these results suggest that the pyrimidine-imidazole thiosemicarbazone may serve as a potential lead scaffold for further development in targeted lung cancer therapy.ADME profiling confirmed the compound’s compliance with Lipinski’s rule of five parameters, supporting its potential as an orally active drug candidate. These findings suggest that our pyrimidine-imidazole thiosemicarbazone represents a promising scaffold for the development of targeted BRAF inhibitors for lung cancer therapy.

  İncele
• MakaleYayıncıda açık erişim2026/r/bayburt/11166
  Shape-Directed Hydrothermal Design of Zinc Oxide Nanoparticles for Antimicrobial and Anticancer Applications

  Özkan, Elvan Hasanoğlu; Yetim, Nurdan Kurnaz; Kızıl, Hamit E.; Öğütçü, Hatice

  The emergence of antibiotic-resistant bacteria represents one of the most pressing challenges in global healthcare. In this study, metal oxide–based nanomaterials are gaining prominence due to their antimicrobial and anticancer potential. In the present study, six new zinc oxide nanoparticles (ZnO-NPs) synthesized via the hydrothermal method using different surfactants were characterized, and their biological activities were evaluated. ZnO-NPs, whose structural properties were determined by a range of analytical methods including BET, FT-IR, SEM-EDX, XRD, and XPS, exhibited significant antibacterial and antifungal effects on a range of bacterial and fungal strains. The study revealed that variations in the morphology and surface area had a direct impact on antimicrobial efficacy. In antimicrobial assays, the inhibition zones ranged from 10.5 mm to 25.5 mm, with ZnO-6 exhibiting the highest efficacy against S. epidermidis (25.5 mm). In cytotoxicity assays, ZnO-6 demonstrated the strongest anticancer potential against H460 cells with the lowest IC50 value of 31.9 µg/mL. Furthermore, a strong correlation was revealed between the physicochemical properties of ZnO-NPs and their anticancer activity, as evidenced by the results of tests conducted on H460 lung cancer cells. Specifically, ZnO-6, which possesses a flower-like morphology and the highest surface area, exhibited the strongest anticancer effect with an IC50 value of 31.9 µg/mL. The parallel enhancement in both antimicrobial and anticancer activities observed in ZnO-6 suggests a common underlying mechanism, likely driven by the high surface area and specific flower-like morphology that facilitates increased interaction with cell membranes and ROS generation. The findings demonstrate that the controlled design of ZnO-NPs in terms of morphology and surface area offers significant potential in both antimicrobial and anticancer applications.

  AtıfScopus3·WoS3

  İncele
• MakaleYalnız künye2026/r/bayburt/11046
  Multi-Pathway Renoprotection by Betanin Against Docetaxel Nephrotoxicity: Modulation of Inflammation, ER Stress, Apoptosis, and Ferroptosis

  Süzen Celbek, Büşra; Akaras, Nurhan; Şimşek, Hasan; Mutlu, Hüseyin; Kızıl, Hamit Emre; Kandemir, Özge; Aygörmez, Serpil; Kandemir, Fatih Mehmet

  Docetaxel (DTX), a cornerstone chemotherapeutic agent, has its clinical utility significantly limited by dose-dependent nephrotoxicity. This study investigated the multi-pathway renoprotective mechanisms of betanin (BTN), a natural antioxidant derived from beetroot, against DTX-induced kidney injury. Male Wistar rats received DTX (30 mg/kg, i.p., single dose) with or without BTN (100 mg/kg/day, p.o.) for 7 days. DTX induced severe renal dysfunction with elevated serum urea and creatinine, and significant oxidative stress characterized by increased MDA and decreased GSH, GPx, SOD, and CAT. Molecular analysis demonstrated widespread upregulation of pro-inflammatory (NF-κB, TNF-α, IL-1β), endoplasmic reticulum stress (PERK, ATF6), pro-apoptotic (Caspase-3, Bax, Apaf-1), and pro-ferroptotic (PTGS2, TfR1) mediators, with concurrent downregulation of protective Bcl-2 and GPx4. Histopathological examination revealed extensive tubular injury, while immunohistochemical analysis showed markedly increased kidney injury marker KIM-1 and decreased aquaporin-1 expression. Remarkably, BTN co-administration significantly attenuated all biochemical, molecular, and structural derangements, restored tissue architecture, and normalized KIM-1 and AQP-1 expression. In conclusion, betanin provides robust, multi-pathway renoprotection against docetaxel-induced nephrotoxicity by concurrently targeting oxidative stress, inflammation, ER stress, apoptosis, and ferroptosis.

  İncele
• MakaleYayıncıda açık erişim2025/r/bayburt/12764
  An Integrated In Vitro and In Silico Investigation of the Bioactive Properties of Wild Glycyrrhiza glabra var. glandulifera

  Kızıl, Hamit Emre; Ulcay, Sibel; Ekincioğlu, Yavuz; Öğütçü, Hatice; Ağar, Güleray

  This investigation examined methanol extracts obtained from the whole plant (encompassing all organs except roots), flowers, and fruits of wild Glycyrrhiza glabra var. glandulifera, a liquorice cultivar indigenous to the Cappadocia region of Türkiye, constituting the first comprehensive in vitro and in silico analysis of this species within the region. Anatomical identification revealed distinctive structural characteristics, including thick-walled epidermal cells in the stem, organized clusters of collenchyma cells, and well-defined sclerenchyma layers encompassing the vascular bundles. The petiole exhibited a characteristic heart-shaped morphology containing three vascular bundles, while foliar analysis demonstrated the presence of stomata on both adaxial and abaxial surfaces, accompanied by a bifacial mesophyll arrangement. The extracts demonstrated remarkable antimicrobial efficacy against both Gram-positive and Gram-negative bacteria, as well as various fungal species. Furthermore, significant cytotoxic activity was observed against non-small cell lung cancer (H460), with the whole plant extract exhibiting IC50 values of 117.8 µg/mL (24 h) and 105.6 µg/mL (48 h). Flower extracts demonstrated IC50 values of 116.8 µg/mL (24 h) and 112.7 µg/mL (48 h), while fruit extracts displayed superior potency with IC50 values of 104.4 µg/mL (24 h) and 63.09 µg/mL (48 h). Molecular docking analyses, conducted utilizing AutoDock Tools 1.5.6 and BIOVIA Discovery Studio Visualizer 4.5, revealed significant protein-ligand interactions, yielding optimal binding energy and inhibition constant values of -9.57 kcal/mol and 96.92 nM, respectively. The RMSD values were calculated based on structural variations between ligand-protein complexes during re-docking procedures. These findings underscore the substantial biological potential of Glycyrrhiza glabra var. glandulifera from Cappadocia, necessitating further comprehensive investigation.

  AtıfScopus6·WoS6

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• MakaleYayıncıda açık erişim2025/r/bayburt/12760
  Pharmacological Potential and Bioactive Components of Wild Anatolian Sage (Salvia aethiopis L.)

  Bilginoğlu, Emine; Kızıl, Hamit Emre; Öğütcü, Hatice; Ağar, Güleray; Bağcı, Yavuz

  Salvia aethiopis L., a member of the Lamiaceae family, has gained attention due to its bioactive compounds with potential therapeutic applications. This study investigated the chemical composition and biological activities of S. aethiopis ethanol extract collected from Karaman province, Türkiye. The phenolic profile of the plant was characterized using LC–MS/MS analysis, which revealed substantial amounts of rosmarinic acid, ferulic acid, caffeic acid, and p-coumaric acid. The antimicrobial activity of the extracts was evaluated against various Gram-positive and Gram-negative bacteria, as well as fungal strains, using the agar well diffusion method. The results demonstrated potent antibacterial effects, particularly against Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. Furthermore, the cytotoxic potential of S. aethiopis was assessed on H-460 non-small cell lung cancer cells. The extract exhibited a dose-dependent cytotoxic effect, with a significant reduction in cell viability after 24 and 48 h of treatment, yielding IC50 values of 80.08 and 56.19 μg/mL, respectively. These findings suggest that S. aethiopis possesses promising antimicrobial and anticancer properties, which could contribute to the development of novel therapeutic agents.

  AtıfScopus8·WoS7

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• MakaleYayıncıda açık erişim2025/r/bayburt/11134
  Dietary Carvacrol Attenuates Cyclophosphamide-Induced Neurotoxicity: Implications for Food-Derived Neuroprotection and Molecular Mechanisms

  Kızıl, Hamit Emre

  Carvacrol (CRV) is a phenolic monoterpene abundant in culinary herbs such as oregano and thyme and is well known for its potent antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the ability of CRV to counteract neurotoxicity induced by cyclophosphamide (CP), a widely used antineoplastic agent. Male Wistar albino rats were divided into five groups and received CP and/or CRV treatments. Neurotoxicity and neuroprotection were evaluated through biochemical assays, real-time PCR, histopathological and immunohistochemical analyses, and behavioral testing (Morris Water Maze). CP administration led to significant increases in oxidative stress markers, disruption of antioxidant enzyme activities, upregulation of inflammatory mediators (NF-κB, TNF-α, iNOS), dysregulation of apoptotic regulators (increased Bax and Casp-3, decreased Bcl-2), alterations in autophagy markers (Beclin-1, LC3A, LC3B), and suppression of Notch1/Hes1 signaling. Histopathological analyses revealed neuronal degeneration, vascular hyperemia, and increased GFAP and 8-OHdG expression in brain tissue. CRV treatment, particularly at higher doses, effectively mitigated these biochemical, molecular, and histological alterations. Notably, CRV administration preserved spatial learning and memory function in CP-treated rats, as demonstrated by the Morris Water Maze test, indicating functional neuroprotection. These findings highlight the multifaceted neuroprotective mechanisms of CRV and suggest its potential as a food-derived bioactive compound for development into functional foods or dietary supplements to improve the quality of life for cancer patients undergoing chemotherapy.

  AtıfScopus10·WoS9

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• MakaleYayıncıda açık erişim2025/r/bayburt/10942
  Biosynthesis of Functionalized Silver Nanomaterials Utilizing Seeds of Black Rosehip (Rosa pimpinellifolia L.) and its Remarkable Antioxidative Capacity

  Kizil, Hamit Emre

  Background: Silver nanoparticles (AgNPs) have gained significant attention due to their unique antimicrobial, catalytic and optical properties. This study focuses on the green synthesis of silver nanoparticles using black rosehip (Rosa pimpinellifolia L.) seeds (Rp-AgNPs) and evaluates their biological activities. Methods: Rp-AgNPs were synthesized using R. pimpinellifolia seed extract and characterized using multiple analytical techniques including UV-Vis spectroscopy, XRD, FTIR, TEM, SEM, EDAX, zeta potential analysis, DSC, SERS and XPS. The biological activities were assessed through DPPH free radical scavenging assay, cytotoxicity testing against H460 lung cancer cells and antimicrobial activity evaluation against various pathogens. Result: The synthesized Rp-AgNPs exhibited spherical morphology with an average size of 51.27 nm and demonstrated stability with a zeta potential of-18.9. The nanoparticles showed enhanced antioxidant activity (IC50 = 30.89 μg/mL) compared to the seed extract (IC50 = 136.4 μg/mL). Cytotoxicity studies revealed significant effects against H460 cells with an IC50 of 65.8 μg/mL. Antimicrobial testing demonstrated effectiveness against both Gram-positive and Gram-negative bacteria (MIC 50-100 μg/mL) and Candida strains (MIC 100-200 μg/mL).

  AtıfScopus1·WoS1

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