Araştırmacılar(11)

• Algul, Oztekin
• Çetin, Gökalp
• Gunesacar, Gulsen
• Merde, Irem Bozbey
• Ozli, Gulsen
• Shirinzadeh, Hanif
• Tasci, Hayrunnisa
• Uysal, Mehtap
• Yaşa, Yaren Zişa
• Yucel, Mehmet Ali
• Zobi, Cengiz

• ArticleYalnız künye2026/r/ebyu/11163
  Asymmetric benzazole derivatives as dual antibiofilm and anti-wall teichoic acid agents against Staphylococcus aureus

  Buga Aktekin, Mine; Oksuz, Zehra; Alagoz, Mehmet Abdullah; Uluca Han, Bahar; Algul, Oztekin

  Aims: Antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), have renewed interest in antivirulence strategies. This study aimed to design, synthesize, and evaluate asymmetric di‑heterocyclic benzazole derivatives as antibiofilm agents targeting wall teichoic acid (WTA) biosynthesis. Materials and methods: Twenty‑one novel bis‑heterocyclic benzazole derivatives bearing an ethyl‑thio linker were synthesized and characterized. Antibacterial activity was determined by broth microdilution. Antibiofilm activity (inhibition and eradication) was assessed at sub‑minimal inhibitory concentrations (sub‑MICs) using crystal violet. Molecular docking and 200 ns molecular dynamics (MD) simulations were performed against key WTA enzymes (TarGH, TarS, TarM, TarL, and TarJ). Results: Compounds 18, 21, 23, and 24 showed potent antibacterial activity against methicillin‑susceptible S. aureus (MSSA) and MRSA, with MIC values as low as 15.62 µg/mL. All selected compounds significantly inhibited biofilm at sub‑MIC levels. Compound 24 was most effective, with an MBIC50 of 3.90 µg/mL against MSSA and eradicated pre‑formed biofilms at 7.81 µg/mL. Docking and MD simulations revealed stable interactions of compounds 23 and 24 with TarGH and TarS, suggesting a WTA‑targeting mechanism. Conclusions: Di‑heterocyclic benzazole derivatives, especially compound 24, are promising scaffolds for antibiofilm agents against S. aureus. Our findings support further mechanistic and preclinical evaluation as potential antivirulence therapeutics.

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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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• ArticleYayıncıda açık erişim2026/r/ebyu/10698
  Experimental and theoretical investigation of a benzazole-2-carboxamide derivative: Crystal structure, spectroscopic characterization, antiproliferative evaluation, and molecular docking studies

  Kılıç, Selçuk; Aktekin, Mine Buga; Turkmenoglu, Burcin; Sert, Yusuf; Caglar, Bulent; Çırak, Çağrı; Algul, Oztekin

  In this study, the structural, spectroscopic, and biological properties of a benzazole-2-carboxamide derivatives, N-(1H-benzo[d]imidazole-2-yl)-4-chlorobenzamide, were comprehensively investigated through both experimental and theoretical approaches. First, the crystal structure of the compound was revealed with the help of single-crystal X-ray diffraction (XRD). Subsequently, density functional theory (DFT) calculations were performed using Gaussian 09 W to optimize the molecular geometry, simulate vibrational spectra, predict nuclear magnetic resonance (NMR) parameters, analyze frontier molecular orbitals HOMO (Highest Occupied Molecular Orbital) - LUMO (Lowest Unoccupied Molecular Orbital), and generate molecular electrostatic potential (MEP) surface maps. To enhance the accuracy of vibrational assignments, potential energy distribution (PED) analysis was conducted via the VEDA4 software. Furthermore, theoretical infrared (IR) and NMR data were compared with experimental results, with results from FT-IR, ¹H-NMR, and ¹³CNMR spectra demonstrating strong agreement and validating the computational models. In addition to spectroscopic characterization, the antiproliferative activity of the synthesized compound against human breast cancer cell line MCF7 and a normal mouse fibroblast cell line (L929) was evaluated. Among the tested compounds, those exhibiting the highest inhibitory activity against MCF7 cells were selected for further analysis. In order to explain the underlying molecular interactions, molecular placement studies were carried out with the help of the Schrödinger Maestro software program, which targets the basic protein binding sites to predict binding affinity and interaction patterns. Collectively, this integrated study provides valuable insights into the structural, spectroscopic, and biological behavior of benzazole-based derivatives, highlighting the synergy between experimental techniques and computational modeling in modern drug discovery research.

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• ArticleAçık Erişim2026/r/ebyu/10622
  Rational design of pyrazole–oxime hybrids as dual-targeting agents for glioma and breast cancer brain metastasis

  Gul, Merve; Alagoz, Mehmet Abdullah; Hepokur, Ceylan; Algul, Oztekin

  To design, synthesize, and biologically evaluate a novel series of 1-(4-chlorophenyl)-2-(4-methylpyrazol-1-yl)ethenone oxime derivatives (5–15) as targeted anticancer agents, focusing on their selectivity for glioma, mechanistic action, and blood–brain barrier (BBB) permeability. The oxime derivatives were synthesized and characterized using 1H-NMR, 13C-NMR, and mass spectrometry. In vitro cytotoxicity was assessed against C6 (glioma), MCF-7 (breast cancer), and SH-SY5Y (human neuroblastoma) cell lines. Flow cytometry evaluated apoptosis and cell cycle arrest for the lead compound. Molecular docking simulations were performed against CDK6 (PDB: 5L2I) and P-glycoprotein/ABCB1 (PDB: 7A6E). All derivatives exhibited selective potency against C6 glioma cells. Compound 14 demonstrated the highest antiproliferative activity (IC₅₀: 31.23 µM) against tumor lines while sparing SH-SY5Y cells. Flow cytometry confirmed that compound 14 triggers apoptosis and induces cell cycle arrest in C6 cells. Molecular docking predicted the most favorable docking scores for compound 14 against both CDK6 and P-glycoprotein. Structure–activity relationships (SAR) analysis validates the 4-methylpyrazole core as a viable scaffold for targeted glioma therapy. These results suggest that further functionalization of the O-alkyl oxime moiety merits further investigation as a starting point for potentially brain-penetrant scaffolds, although in vivo and target-level validation are required.

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• ArticleYalnız künye2026/r/ebyu/10364
  Development of pyridazinone derivatives linked ethyl-bridged-1,2,4-triazole for potential cancer therapy

  Bozbey Merde, İrem; Aykaç, Okan; Hepokur, Ceylan; Yaşa, Yaren Zişa; Taşkor Önel, Gülce; Türkmenoğlu, Burçin

  A series of novel pyridazinone derivatives linked ethyl-bridged-1,2,4-triazole were synthesized starting from p-chloroacetophenone. The chemical structures of the compounds 5(a-f) were identified by 1HNMR, 13CNMR and LC-QTOF-MS analysis. In this study, the DDPH method was used to evaluate the antioxidant properties of the compounds. The anticancer activity of the compounds was investigated by MTT method in MCF-7, MDA-MB-231 and L929 cell lines. Gene expression levels of Bcl2, Bax and Casp9 genes were compared, and stages of cell death were determined with high accuracy by flow cytometry. Since compound 5a showed promising cytotoxic effects, molecular docking study was performed to support these results and binding values against Bcl2 anti-apoptotic (PDB ID: 6QGG), Bcl-2 (PDB ID: 4IEH) and tubulin regulation (PDB ID: 1SA0) targets were calculated.

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• Review ArticleYayıncıda açık erişim2025/r/ebyu/12184
  The Significance of Mono- and Dual-Effective Agents in the Development of New Antifungal Strategies

  Zobi, Cengiz; Algul, Oztekin

  Invasive fungal infections (IFIs) pose significant challenges in clinical settings, particularly due to their high morbidity and mortality rates. The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies. Current antifungal drugs target the fungal cell membrane, cell wall, or intracellular components, but resistance mechanisms such as altered drug-target interactions, enhanced efflux, and adaptive cellular responses have diminished their efficacy. Recent research has highlighted the potential of dual inhibitors that simultaneously target multiple pathways or enzymes involved in fungal growth and survival. Combining pharmacophores, such as lanosterol 14α-demethylase (CYP51), heat shock protein 90 (HSP90), histone deacetylase (HDAC), and squalene epoxidase (SE) inhibitors, has led to the development of compounds with enhanced antifungal activity and reduced resistance. This dual-target approach, along with novel chemical scaffolds, not only represents a promising strategy for combating antifungal resistance but is also being utilized in the development of anticancer agents. This review explores the development of new antifungal agents that employ mono-, dual-, or multi-target strategies to combat IFIs. We discuss emerging antifungal targets, resistance mechanisms, and innovative therapeutic approaches that offer hope in managing these challenging infections.

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• ArticleYayıncıda açık erişim2025/r/ebyu/12070
  Pyrrole-Tethered Bisbenzoxazole Derivatives: Apoptosis-Inducing Agents Targeting Breast Cancer Cells

  Kuzu, Burak; Yetkin, Derya; Hepokur, Ceylan; Algul, Oztekin

  This study presents the design, synthesis, and biological evaluation of a series of novel pyrrole-tethered bisbenzoxazole (PTB) derivatives as potential apoptosis-inducing agents targeting the MCF-7 human breast cancer cell line. The anticancer activity of these compounds was evaluated in vitro using the MTT assay, with tamoxifen serving as the reference therapeutic agent. Compounds B8, B14, and B18 demonstrated remarkable cytotoxicity against MCF-7 cells, exhibiting approximately 8-fold lower IC50 values compared to tamoxifen, while showing minimal effects on healthy fibroblasts. Further investigations revealed that these compounds effectively induced early-stage apoptosis and selectively arrested the cell cycle at the G1 phase in cancer cells. Gene expression analysis confirmed selective activation of the caspase-9-mediated apoptotic pathway in MCF-7 cells, providing insights into their underlying molecular mechanisms. These findings highlight the promising potential of PTB derivatives as potent anticancer agents, laying the groundwork for the development of targeted therapies for breast cancer that leverage apoptosis induction for improved therapeutic outcomes.

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• ArticleAçık Erişim2025/r/ebyu/11987
  Structure-based inhibition of acetylcholinesterase and butyrylcholinesterase with 2-Aryl-6-carboxamide benzoxazole derivatives: synthesis, enzymatic assay, and in silico studies

  Kuzu, Burak; Alagoz, M. Abdullah; Demir, Yeliz; Gulcin, Ilhami; Burmaoglu, Serdar; Algul, Oztekin

  An important research topic is the discovery of multifunctional compounds targeting different disease-causing components. This research aimed to design and synthesize a series of 2-aryl-6-carboxamide benzoxazole derivatives that inhibit cholinesterases on both the peripheral anionic and catalytic anionic sides. Compounds (7–48) were prepared from 4-amino-3-hydroxybenzoic acid in three steps. The Ellman test, molecular docking with Maestro, and molecular dynamics simulation studies with Desmond were done (Schrodinger, 12.8.117). Compound 36, the most potent compound among the 42 new compounds synthesized, had an inhibitory concentration of IC50 12.62 nM for AChE and IC50 25.45 nM for BChE (whereas donepezil was 69.3 nM and 63.0 nM, respectively). Additionally, compound 36 had docking values ​​of − 7.29 kcal/mol for AChE and − 6.71 kcal/mol for BChE (whereas donepezil was − 6.49 kcal/mol and − 5.057 kcal/mol, respectively). Furthermore, molecular dynamics simulations revealed that compound 36 is stable in the active gorges of both AChE (average RMSD: 1.98 Å) and BChE (average RMSD: 2.2 Å) (donepezil had average RMSD: 1.65 Å and 2.7 Å, respectively). The results show that compound 36 is a potent, selective, mixed-type dual inhibitor of both acetylcholinesterase and butyrylcholinesterase. It does this by binding to both the catalytically active and peripheral anionic sites of cholinesterases at the same time. These findings show that target compounds may be useful for establishing the structural basis for new anti-Alzheimer agents.

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• ArticleYalnız künye2025/r/ebyu/11965
  Substituted bisbenzimidazole derivatives as multiple targeting agents to treat Alzheimer's disease, diabetes, and microbial infections

  Algul, Oztekin; Mete, Burak; Turkmenoglu, Burcin; Saglamtas, Ruya; Alagoz, M.Abdullah; Dogen, Aylin; Gulcin, Ilhami; Burmaoglu, Serdar

  This study presents the synthesis and bioactivity screening of a series of substituted bisbenzimidazoles (3a–l), assessed for their inhibitory effects on α-glycosidase, α-amylase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), as well as their antibacterial activities and metal chelation properties. Compound 3e exhibited the most significant inhibitory activity against intestinal α-glycosidase and α-amylase, showing IC50 values of 15.51 µM and 18.18 µM, respectively. All bisbenzimidazole derivatives demonstrated significant inhibitory activities, with Ki values between 0.99 and 2.98 nM for AChE and 0.40 to 2.18 nM for BChE. Antimicrobial analyses revealed significant antibacterial efficacy in compounds 3c and 3f, with IC50 values ranging from 10.75 to 12.83 μg/μL. This article presents a thorough evaluation of the pharmacological activities associated with bisbenzimidazole compounds 3a–l. To validate experimental results, selected compounds exhibiting notable enzyme inhibitory potential were subjected to molecular docking studies, which demonstrated their binding interactions within the active sites of target enzymes. Molecular dynamics simulation studies were carried out for 100 ns to determine the stability of the compounds in target proteins. During the simulation, it was observed that 3 h, 3 g, 3l, and 3e were stable in 4EY7, 4BDS, 3TOP, and 2QV4, respectively. Compounds 3 h, 3 g, 3e, and 3l have been identified as promising candidates for the inhibition of AChE, BChE, α-glycosidase, and α-amylase, respectively.

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• ArticleYalnız künye2025/r/ebyu/11509
  Synthesis and evaluation of sulfonamide-chalcone hybrid compounds as inhibitors of VEGFR1/VEGFR2-mediated angiogenesis

  Barlak, Neslisah; Sanli, Fatma; Celik, Suleyman; İskender, Burhan; Anil, Derya Aktas; Gambacorta, Nicola; Burmaoglu, Serdar; Nicolotti, Orazio; Algul, Oztekin; Karatas, Omer Faruk

  Cancer continues to be a major worldwide health concern, with angiogenesis playing a pivotal role in its progression and metastasis. The capacity of tumors to induce angiogenesis is crucial for their proliferation and metastasis, rendering it a significant target for treatment strategies. This study involved the synthesis of sulfonamide-chalcone hybrid compounds and the evaluation of their anti-angiogenic activity by the assessment of their effects on vascular endothelial growth factor receptors (VEGFR1/VEGFR2) in human umbilical vein endothelial cells (HUVECs). Among the synthesized compounds, 28 and 31 exhibited the most promising inhibitory effects similar to sorafenib as positive control, with IC50 values superior to 10 μM. They dramatically diminished endothelial cell proliferation and tube formation without exhibiting significant cytotoxicity against healthy human cells. Molecular docking simulations validated their binding affinity to VEGFR1/VEGFR2 receptors, elucidating their molecular mechanisms. Moreover, compounds 28 and 31 exhibited significant anti-angiogenic activity in both 2D and 3D angiogenesis assays, indicating their potential as novel anti-cancer agents. These findings underscore the therapeutic potential of these compounds in blocking angiogenesis and necessitate additional in vivo research to confirm their clinical relevance.

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