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Öğe Assessing the Antiangiogenic Effects of Chalcones and Their Derivatives(Taylor & Francis Ltd, 2024) Burmaoglu, Serdar; Gobek, Arzu; Anil, Derya Aktas; Alagoz, Mehmet Abdullah; Guner, Adem; Guler, Cem; Hepokur, CeylanPathological angiogenesis plays a critical role in tumorigenesis and tumor progression, and anti-angiogenesis therapies have evinced promising antitumor effects in solid tumors. Chalcone skeleton has been regarded as a potential antitumor agent that also targets angiogenesis. In this study, we designed twenty-one non-fluoro-substituted chalcones (13-18, 24-27) and saturated chalcone derivatives (19-23, 28-33) as anti-angiogenic compounds. During the initial stage, these compounds were assessed for their anti-cancer activities against MCF-7 cancer cell lines according to the MTT assay. The compounds revealed satisfactory anti-proliferative capability. An ex vivo fertilized hens' egg-chorioallantoic membrane (HET-CAM) angiogenic study was conducted for the compounds to gauge their mortality and toxicity, which, in turn, revealed a potent anti-angiogenic effect. Eight compounds (16, 17, 21, 24, 26, 27, 29, and 31) significantly reduced densities of capillaries on CAM, whereas compounds 27 and 29 were the most effective anti-angiogenic agents, when compared with Suramin. Moreover, RT-qPCR analysis demonstrated that the anti-angiogenic activity was associated with the fold changes of VEGFR2. Molecular docking studies were conducted for compounds to investigate their mode of interaction within the binding site of VEGFR-2 kinases. This work provided a basis for further design, structural modification, and development of chalcone derivatives as new anti-angiogenic agents.Öğe Benzoxazole Derivatives as Dual p38α Mitogen-Activated Protein Kinase and Acetylcholinesterase Inhibitors: Design, Synthesis, and Evaluation for Alzheimer's Disease and Cancer Therapy(Wiley-V C H Verlag Gmbh, 2025) Zoatier, Bayan; Yildiztekin, Gizem; Alagoz, Mehmet Abdullah; Hepokur, Ceylan; Dilek, Esra; Algul, OztekinAlzheimer's disease (AD), the most prevalent form of dementia, leads to progressive cognitive decline due to pathological hallmarks including amyloid plaques, neurofibrillary tangles, synaptic loss, neuroinflammation, and neuronal cell death, highlighting the urgent need for multitarget therapeutic strategies. The p38 alpha mitogen-activated protein kinase (p38 alpha MAPK) pathway is a key regulator of neuroinflammation and has been implicated in AD pathogenesis. Additionally, dysregulation of p38 alpha MAPK is associated with tumorigenesis, making it a promising target for both neurodegenerative and proliferative diseases. In this article, a series of benzoxazole derivatives is designed and synthesized to evaluate their dual inhibitory potential against p38 alpha MAPK and acetylcholinesterase (AChE), aiming for a multifaceted therapeutic approach to AD. A total of 31 compounds are synthesized and assessed for their antiproliferative activity, p38 alpha MAPK inhibition, and AChE inhibitory effects. In vitro assays demonstrate that several compounds exhibit potent dual inhibition of p38 alpha MAPK and AChE, while molecular docking studies provide insights into their binding interactions within the active sites. These findings suggest that benzoxazole-based scaffolds offer a promising framework for the development of dual-acting inhibitors targeting both neuroinflammation and tumorigenesis. Further in vivo and mechanistic studies are warranted to explore their therapeutic potential.Öğe Chemical composition, and antioxidant, antimicrobial, and cytotoxicity properties of Silene latifolia(Springer International Publishing, 2026) Gökkaya, İçim; Hepokur, Ceylan; Aykaç, Okan; Ulama, Sena Nur; Bal, Halil; Cakir, Oğuz; Tarhan, AbbasSilene species have various pharmacological properties, including antimicrobial, antioxidant, anti-inflammatory, antitumoral, adaptogenic, immunomodulatory, hepatoprotective, and cytotoxic activities. This study assessed the antibacterial, antioxidant, and cytotoxic activities and the chemical profile of crude methanol extract and sub-extracts prepared from the aerial parts of Silene latifolia for the first time. After a 24-h incubation, the methanol extract exhibited the highest activity against MCF-7 cancer cell line (IC50: 19.25 ± 0.05 µg/mL), whereas the water sub-extract showed the greatest activity against MDA-MB-231 cancer cell line (IC50: 15.20 ± 0.47 µg/mL). After a 48-h incubation, the extracts having the strongest cytotoxic effects against MCF-7 and MDA-MB-231 cells were the water sub-extract (IC50: 14.52 ± 0.86 µg/mL) and the methanol crude extract (IC50: 12.08 ± 0.78 µg/mL), respectively. The methanol extract exhibited the most potent radical-scavenging activity, enhancing total antioxidant status and reducing total oxidant status. The extracts had no antibacterial or antifungal activity against the tested microorganisms. GC–MS analysis revealed that oleic acid, elaidic acid, palmitic acid, and their derivatives were abundant in sub-extracts. The LC–MS/MS analysis demonstrated that the water sub-extract included fumaric acid, quinic acid, aconitic acid, acacetin, and luteolin. This study highlighted that S. latifolia exhibited high antioxidant activity, and that it had a potent cytotoxic effect against breast cancer cells with a high selectivity index. © The Author(s), under exclusive license to Società Botanica Italiana onlus 2026.Öğe Cytotoxic effect of azole compounds bearing trifluorophenyl ring on MCF-7, MDA-MB-231, and HCT-116 cancer cell line(2022) Alagöz, Mehmet; Özdemir, Zeynep; Hepokur, Ceylan; Karakurt, ArzuCancer, a disease defined by rapid proliferation of cells, still remains one of the most feared diseases of the modern world. Many structurally different anti-carcinogenic drugs are used in several tumor types such as bladder, colon, ovary, breast, head and neck, testis, lung and prostate cancer. In this study, cytotoxic effects of the compounds with different linkers (ketone, oxime, alcohol, chlorine) between pyrazole and trifluoromethyl on MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human breast adenocarcinoma), and HCT-116 (human colon cancer) cell lines were investigated. Compound a1 was observed to be the most potent compound with IC50 values of 5.84±0.76, 5.01±0.32, 5.57±0.02 µg.ml-1 against these cell lines, respectively. It was found that all compounds were very effective against all the tested cancer cell lines.Öğe Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells(Wiley-V C H Verlag Gmbh, 2025) Zoatier, Bayan; Yildiztekin, K. Gizem; Alagoz, M. Abdullah; Hepokur, Ceylan; Burmaoglu, Serdar; Algul, OztekinType V MAPK inhibitors are distinguished by their capacity to target both the ATP binding site and a specific allosteric site on the enzyme. The present work utilized in silico analysis with Maestro 13.8.135 (Schrodinger) software in conjunction with experimental investigations to enhance the antiproliferative efficacy and forecast the likely mechanism of action of benzothiazole derivatives. Approximately 28 compounds were developed, produced, and assessed for their antiproliferative properties against two breast cancer cell lines: ER+ (MCF7) and ER- (MDA-MB-231), in addition to one normal mouse fibroblast cell line (L929). Their antiproliferative activities were evaluated via the MTT test, with doxorubicin and cisplatin serving as reference drugs for comparison. Consequently, the compounds with the greatest activity against the MCF7 cell line were chosen, and their inhibitory effects on the p38 alpha MAPK enzyme were examined. The molecular docking studies of compounds 15 and 19 demonstrated significant binding affinities for p38 alpha MAPK. Molecular dynamics simulations conducted over 100 ns revealed that compounds 15 and 19 exhibit stability inside both the ATP-binding domain and the lipid domain of p38 alpha MAPK. The research focused on creating effective Type V MAPK inhibitors demonstrate that compounds 15 and 19 possess considerable ability to inhibit p38 alpha MAPK, hence establishing them as promising anticancer agents.Öğe Development of pyridazinone derivatives linked ethyl-bridged-1,2,4-triazole for potential cancer therapy(Elsevier, 2026) Merde, Irem Bozbey; Aykac, Okan; Hepokur, Ceylan; Yasa, Yaren Zisa; Onel, Gulce Taskor; Turkmenoglu, BurcinA series of novel pyridazinone derivatives linked ethyl-bridged-1,2,4-triazole were synthesized starting from pchloroacetophenone. 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.Öğe In silico investigation of the efficacy of benzopyrazine derivatives on breast cancer by VEGFR2 inhibition using ML/DL based CADD software(Elsevier Science Inc, 2026) Merde, Irem Bozbey; Aykac, Okan; Hepokur, Ceylan; Kabier, Muzammil; Ortaakarsu, Ahmet BugraAngiogenesis is a critical pathway for cancer; The formation of new blood vessels is essential for the growth and metastasis of tumors. VEGF and its receptor VEGFR also play important roles in angiogenesis. VEGFR2 stands out as an important therapeutic target for breast cancer treatment. In this study, the interaction between benzopyrazine derivatives and VEGFR2 was evaluated using computer-based drug design (CADD) models, bioinformatics analyses and complementary computational methods. Biological activity predictions were made by developing the interaction data of 49 benzopyrazine-derived compounds in a virtual environment and by developing a QSAR model. Binding stability of proteins in newly designed structures was demonstrated with molecular dynamics simulations. ADMET predictions reveal that these tables have appropriate pharmacokinetic metabolism. Synthesizability of compounds with the best docking scores was calculated with artificial intelligence using the Retroscheme software. For compound number 46, which has the highest potential, molecular dynamics simulation data for 500 ns were calculated via the Desmond interface and its binding was interpreted. The study particularly shows that compound 46 may be an effective VEGFR2 inhibitor in the treatment of breast cancer.Öğe In Vitro and In Silico Evaluation of the Combined Effects of Glycyrrhizic Acid and Ciprofloxacin on DNA Gyrase Activity in Staphylococcus aureus(Wiley-V C H Verlag Gmbh, 2026) Aykac, Okan; Bozbey Merde, Irem; Bal, Halil; Ortaakarsu, Ahmet Bugra; Hepokur, Ceylan; Berk, NecmettinThe emergence of antibiotic-resistant strains of Staphylococcus aureus underscores the urgent need for novel therapeutic strategies. This study evaluates the in vitro antibacterial, antioxidant, and cytotoxic properties of glycyrrhizic acid (GA) in combination with ciprofloxacin (CIP) against S. aureus ATCC 25923. Antimicrobial activity was determined using broth microdilution and checkerboard assays, revealing MIC values of 0.25 & micro;g/mL for CIP and 512 & micro;g/mL for GA. The GA-CIP combination exhibited an additive effect (FICI = 1). Cytotoxicity assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on L929 cells demonstrated acceptable IC50 values for each agent and their combination. Antioxidant capacity was measured using alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH), total antioxidant level (TAS), and total oxidant level (TOS) assays, with GA showing potential to mitigate CIP-induced oxidative stress. In silico molecular docking studies targeting DNA gyrase (PDB ID: 2XCT) supported a plausible binding synergy between GA and CIP. These findings suggest that GA, when combined with CIP, may enhance antibacterial efficacy and reduce oxidative damage, representing a promising strategy to address antibiotic resistance in S. aureus.Öğe Investigating the Cytotoxic Potential of Omphalodes cappadocica (Willd.) DC. on Breast Cancer Cells by Phytochemical-Based Molecular Docking Studies: A Comparative Study of Aerial Parts and Roots(Wiley-V C H Verlag Gmbh, 2026) Gokkaya, Icim; Hepokur, Ceylan; Aykac, Okan; Karaman, Elif; Cakir, Oguz; Tarhan, Abbas; Yilmaz, Mustafa AbdullahThis study aims to evaluate the potential effects of Omphalodes cappadocica on a breast cancer cell line for the first time. The methanol extract of the aerial parts (Ae-M) exhibited the strongest cytotoxicity against MCF-7 and MDA-MB-231 cells after 48 h of incubation, with IC50 values of 14.08 +/- 0.05 and 10.63 +/- 0.01 mu g/mL, respectively. The root methanol extract (Ro-M) exhibited significant activity in the MCF-7 and MDA-MB-231 cell lines during 48 h of incubation, with IC50 values of 19.25 +/- 0.66 and 16.38 +/- 0.02 mu g/mL, respectively. Quantitative analysis by LC-MS/MS revealed that the main constituents of Ae-M were rosmarinic, quinic, and vanillic acids. Quinic and fumaric acids were identified in Ro-M. Quinic acid had a strong affinity for the target proteins PDB 3ERT, PDB 3HNG, and PDB 3KMU, with docking scores of -9.2, -7.8, and -6.6 kcal/mol, respectively. The docking score for rosmarinic acid for the target protein PDB 3HNG was determined to be -9.7 kcal/mol. The findings suggest that O. cappadocica may serve as a source for the development of anticancer agents.Öğe Phytochemical Characterization, Cytotoxic, and Antimicrobial Properties of Aerial Parts of Heliotropium hirsutissimum Weber: In Vitro and In Silico Approaches(Wiley-V C H Verlag Gmbh, 2026) Gokkaya, Icim; Aykac, Okan; Hepokur, Ceylan; Bal, Halil; Polat, Derya Cicek; Renda, Gulin; Yilmaz, Mustafa AbdullahThis study evaluated the possible cytotoxic properties of the aerial parts of Heliotropium hirsutissimum Weber on MCF-7 and MDA-MB-231 breast cancer cell lines and also investigated its antimicrobial effects. Following the identification of the main components of the extract using gas chromatography-mass spectrometry analysis, molecular docking studies were performed using the PDB 6YD9 and PDB 6BRX targets. The crude methanol extract exhibited the most significant cytotoxicity against the MCF-7 and MDA-MB-231 cell lines, with IC50 values of 10.03 +/- 0.02 and 14.36 +/- 0.65 mu g/mL, respectively. Among the tested extracts, the n-hexane sub-extract had modest efficacy against Staphylococcus aureus and Bacillus cereus, with a minimum inhibitory concentration of 0.625 mg/mL. In silico studies demonstrated that 3'-acetyllycopsamine and heliotrine had moderate affinity for the PDB 6YD9 target residue regions, with docking scores of -6.7 and -6.5 kcal/mol, respectively. The docking scores for 3'-acetyllycopsamine and heliotrine against PDB 6BRX were -6.7 and -6.6, respectively. Quinic acid showed strong affinity for the target residues in PDB 6YD9 and PDB 6BRX, with docking scores of -9.3 and -12.1 kcal/mol, respectively. This study suggests that H. hirsutissimum may have a potential effect on breast cancer. This effect may be attributed to the phenolic compounds and pyrrolizidine alkaloids. These findings indicate that H. hirsutissimum is a promising natural resource for future research in both the anticancer and antimicrobial fields.Öğe Synthesis of New 1-Aryl-2-(3,5-dimethylpyrazol-1-yl)ethanone Oxime Ether Derivatives and Investigation of Their Cytotoxic Effects(Mdpi, 2021) Alagoz, Mehmet Abdullah; Karakurt, Arzu; Hepokur, Ceylan; Salva, Emine; Onkol, Tijen; Ghoneim, Mohammed M.; Abdelgawad, Mohamed A.In this study, 12 new 1-aryl-2-(3,5-dimethylpyrazol-1-yl)ethanone oxime ether derivatives were designed and synthesized to investigate their cytotoxic effects. The in vitro cytotoxic activities of the compounds were evaluated against cervix, colon, breast, glioma, neuroblastoma, and lung cancer cell lines, as well as a healthy cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide (MTT) assays with 5-fluorouracil (5-FU) as the reference compound. Compound 5f (IC50 = 5.13 mu M) was found to be more effective than 5-FU (IC50 = 8.34 mu M) in the C6 cancer cell line, and it had no cytotoxic effect on the L929 healthy cell line. Flow cytometry was used to investigate the mechanism of action of compound 5f on the cell cycle of the C6 cell line. The analysis showed that cell death was significantly due to apoptosis. These results indicate that compound 5f induces cell cycle arrest, and may be effective in treating glioma.Öğe Synthesis, Biological Evaluation and In Silico Studies of Some 2-Substituted Benzoxazole Derivatives as Potential Anticancer Agents to Breast Cancer(Wiley-V C H Verlag Gmbh, 2022) Kuzu, Burak; Hepokur, Ceylan; Alagoz, Mehmet Abdullah; Burmaoglu, Serdar; Algul, OztekinIn an attempt to develop potent and selective anticancer agents, some 5- or 6- and N-substituted benzoxazol-2-carboxamide derivatives were designed, synthesized, and evaluated for their cyclooxygenase inhibitory, antioxidant, and anti-proliferative activity against MCF-7 and MDA-MB-231 cell lines. Among them 5-OMe, N-piperidine substituted (compound 30), 5-OMe, N-4-methylpiperidine substituted (compound 31) and 5-Cl, N-piperidine substituted (compound 34) benzoxazole 2-carboxamide compounds have a moderate inhibitory effect in COX-1 and COX-2 enzymes. Anti-proliferative studies show that compound 30 (IC50=5.35 mu M) and compound 31 (IC50=5.82 mu M) have similar activity to reference drug 5-FU (IC50=3.95 mu M) on MCF-7 cell but they have lower toxic effect for healthy WI-38 cell line. For the MCF-7 cell line, compounds 30 and 31 show approximately 1.5 times higher selectivity compared to the 5-FU control. Among the synthesized compounds 30, 31, and 34 had the best anti-proliferative effect and were used to perform flow cytometry and cell cycle analysis on MCF-7 cell line. To predict the binding modes and pharmacokinetic parameters of all compounds, in silico studies were carried out. These compounds may shed light on cancer treatment and cancer research.
