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Öğe Evaluation of Antiproliferative Activity and Molecular Modeling Studies of Some Novel Benzimidazolone-Bridged Hybrid Compounds(Mdpi, 2025) Guven, Okan; Mentese, Emre; Yilmaz, Fatih; Guner, Adem; Emirik, Mustafa; Caliskan, NedimeBackground/Objectives: Cancer is among the leading causes of mortality worldwide. In 2022 alone, the global cancer death toll stood at 9.74 million. Projections indicate that this figure will rise to 10.4 million by 2025. Methods: A new series of benzimidazolone-bridged hybrid compounds containing thiophene, furan, oxadiazole, piperazine, and coumarin moieties was synthesized and structurally characterized by 1H-NMR, 13C-NMR (APT), and elemental analysis. Their cytotoxic effects were evaluated by MTT assay against human lung (A549), human breast (MCF-7), and human cervical (HeLa) cancer cell lines, and the non-cancerous HEK293 cell line after 48 h exposure over a concentration range of 0.5-250 mu M. IC50 values were determined, and Selectivity Indexes (SI) were calculated using HEK293 as the reference normal cell line. Molecular docking studies were carried out using the Glide XP protocol against VEGFR2 (PDB ID: 4ASD) and CDK4-Cyclin D3 (PDB ID: 7SJ3), with sorafenib and abemaciclib as reference inhibitors. Results: The results of anticancer activity were compared with doxorubicin (IC50 +/- SD (mu M)/SI: 4.3 +/- 0.2/1.20 for A549, 6.4 +/- 0.37/0.77 for MCF-7, 3.4 +/- 0.19/1.54 for HeLa), a drug used for cancer chemotherapy. The structures of the newly synthesized hybrid compounds were identified by 1H-NMR, 13C-NMR (APT), and elemental analysis data. These hybrid compounds represent a promising class of anticancer agents. Several compounds demonstrated marked and concentration-dependent cytotoxicity across all cancer cell lines, with HeLa cells showing the highest overall sensitivity. The introduction of an oxadiazole ring (compound 7) and coumarin substituents (compounds 12b-12d) markedly improved anticancer activity and selectivity, yielding low-micromolar IC50 values in HeLa cells (10.6-13.6 mu M) and high Selectivity Indexes (SI = 2.0-3.63). Compound 6 also exhibited balanced potency across A549, MCF-7, and HeLa cells (IC50 = 28.3-31.2 mu M) with SI values >= 2.0. Compound 9 showed strong cytotoxicity across all cancer cell lines; its moderate SI values indicate lower discrimination between malignant and non-malignant cells. Taken together, these findings identified compounds 7, 12b-12d, 6, and 12c as the most promising benzimidazolone-based candidates, displaying both potent cytotoxicity and favorable selectivity over non-malignant HEK293 cells. Conclusions: Among the synthesized molecules, the oxadiazole derivative (7) and the coumarin-based hybrids (12b-12d) exhibited the strongest combination of cytotoxic activity and selectivity, reflected by their low IC50 values and high SI ratios. Notably, compound 12c combined strong biological activity with the highest predicted VEGFR2 affinity in the series, highlighting it as a particularly promising scaffold. While compound 9 exhibited excellent docking scores toward both VEGFR2 and CDK4, its lower selectivity suggests a need for further structural refinement. Overall, the biological and computational findings converge to identify these benzimidazolone hybrids as credible lead candidates for future anticancer optimization.Öğe New 1,3,4-thiadiazol derivatives: Synthesis, computational study and X-Ray(Elsevier, 2020) Unluer, Dilek; Dugdu, Esra; Emirik, Mustafa; Sahin, Onur; Unver, Yasemin; Sancak, KemalIn this study, 4-hydroxyphenyl-3H-1,2,4-triazol-3-one derivatives (la-d), cyanomethoxyphenyl-3-alkyl/aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-acetonitriles (2a-d) and bis amino-1,3,4-thiadiazol-5-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazol-3-one (3a-d) were synthesized. The new compounds were characterized by elemental analyses, IR, H-1 NMR, C-13 NMR and mass spectral studies. The molecular structure of compound 2c was determined by X-ray diffraction. Vibrational data, H-1 NMR and C-13 NMR chemical shifts of compound 3 b were obtained by DET/B3LYP/6-311++G(d,p) method and theoretical spectral data were compared with the experimental ones. Furthermore, Gauswiev 5.0 was used to visualize the results of the computation MEP surface for compound 3 b. (C) 2020 Elsevier B.V. All rights reserved.Öğe Novel Adenine-Hydrazone Hybrids Against Human Lung Adenocarcinoma (A549): Design, Synthesis, Cellular Mechanistic Investigation and Molecular Docking Studies(Mdpi, 2026) Mentese, Emre; Caliskan, Nedime; Aksu, Didem; Emirik, Mustafa; Guner, Adem; Yilmaz, FatihBackground/Objectives: Adenine derivatives are promising anticancer scaffolds, but their cellular mechanisms remain unclear. This study aimed to synthesize adenine-hydrazone hybrids and evaluate their cytotoxic effects in human lung adenocarcinoma (A549) cells. Methods: A series of adenine-hydrazone compounds (3a-r) was synthesized and tested for cytotoxicity in A549 and MRC-5 cells. Selected compounds were further analyzed for LDH release, oxidative stress markers, ROS production, mitochondrial membrane potential, cell-cycle distribution, apoptosis, and in silico docking against VEGFR2, ALK5, and EGFR. Results: Compounds with electron-withdrawing or donor-acceptor substituents showed the highest cytotoxicity, while halogenated and methoxy analogs were moderately active. Among the synthesized derivatives, 4F-substituted derivatives (3c) showed more activity than 2F- and 3F-substituted ones (3a and 3b). 4F- and 3Br-substituted derivatives (3f) showed more activity than only 4F-substituted ones (3c). 4-Nitro-substituted derivative (3i) showed more activity than 4F- (3c), 4Cl- (3d) and 4OMe- (3h) derivatives. Trimethoxy-substituted derivative (3l) showed more activity than di- and mono-substituted methoxy derivatives (3g, 3h, 3j and 3k). Among the salicyl aldehydederivatives (3m-r), 4-N(et)2-substituted derivative (3r) showed more activity than non-substituted (3m), 5Br-(3n), 5Cl-(3o), 5Me (3p) and 3OCH3 (3q) derivatives. Treatment induced oxidative stress, mitochondrial depolarization, Sub-G1 cell-cycle accumulation, and apoptosis. Docking studies indicated strong binding to VEGFR2 and ALK5, suggesting dual inhibition as a potential mechanism. Conclusions: Adenine-hydrazone derivatives exert substituent-dependent anticancer effects by inducing redox imbalance-associated mitochondrial dysfunction and regulated cell death. These results highlight their potential as lead structures for lung cancer therapy.Öğe Production and characterization of activated carbon foams with various activation agents for electrochemical double layer capacitors (EDLCs) applications(Elsevier, 2024) Ozcifci, Zehra; Emirik, Mustafa; Akcay, Hakki Turker; Yumak, TugrulSucrose-based activated carbons were obtained by carbon foams with sugar and cobalt (II) nitrate as precursors, followed by using different chemical activation agents. The effect of Co(NO3)2 concentration, the carbonization temperature and the activation agent on the surface chemistry, porosity were investigated. Textural characterization and electrochemical tests were performed on the activated carbon samples (CF). The results showed that the activated carbon produced by H2SO4 and KOH at 800 degrees C had a surface area of 691 m2/g and 1125 m2/g, 89% and 80% of the sample pore structure was microporous, and specific capacitance of 8.4 F/g and 162.2 F/g at a constant current density of 250 mA/g, respectively. K2CO3-activated carbon had 918 m2/g surface area and 63% of the sample pore structure with microporous and 1.4 F/g specific capacitance, H3PO4-activated carbon and ZnCl2-activated carbon had 1833 m2/g and 1597 m2/g surface area, 53% mesoporous and 50% mesoporous, 222.4 F/g and 149.9 F/g specific capacitance respectively. The most promosing result was observed in the electrochemical storage behavior of the carbon materials with hierarchical pore structure activated with H3PO4 is associated with increasing defect zones at the edges of micro- and mesoporous morphology, resulting in a higher surface area and increased conductivity of the material.
