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Öğe Bovine carbonic anhydrase (bCA) inhibitors: Synthesis, molecular docking and theoretical studies of bisoxadiazole-substituted sulfonamide derivatives(Elsevier, 2024) Eybek, Abdulbaki; Kaya, Mustafa Oguzhan; Gulec, Ozcan; Demirci, Tuna; Musatat, Ahmad Badreddin; Ozdemir, Oguzhan; Oner, Mine Nazan KerimakThis paper describes the in vitro inhibition potential of bisoxadiazole-substituted sulfonamide derivatives (6a-t) against bovine carbonic anhydrase (bCA) after they were designed through computational analyses and evaluated the predicted interaction via molecular docking. First, in silico ADMET predictions and physicochemical property analysis of the compounds provided insights into solubility and permeability, then density functional theory (DFT) calculations were performed to analyse their ionization energies, nucleophilicity, in vitro electron affinity, dipole moments and molecular interactions under vacuum and dimethyl sulfoxide (DMSO) conditions. After calculating the theoretical inhibition constants, IC50 values determined from enzymatic inhibition were found between 12.93 and 45.77 mu M. Molecular docking evaluation revealed favorable hydrogen bonding and pi-interactions of the compounds within the bCA active site. The experimentally most active compound, 6p, exhibited the strongest inhibitory activity with a theoretical inhibition constant value of 9.41 nM and H-bonds with Gln91, Thr198, and Trp4 residues and His63 Pi-cation interactions with His63 residues. Overall, the study reveals promising bCA blocking potential for the synthesized derivatives, similar to acetazolamide.Öğe Cholesterol functionalized linear Poly(ε-caprolactone) polymers: Effects of chain length on mesomorphic and dielectric properties(Elsevier Science Sa, 2025) Doganci, Merve Dandan; Davarci, Derya; Uner, Melek; Demir, Ahmet; Musatat, Ahmad Badreddin; Akdogan, Mustafa; Doganci, ErdincCholesterol-functionalized linear poly (epsilon-caprolactone) (Chol-PCL) polymers with different chain lengths (n = 10, 20, 30, and 70) were successfully synthesized via a ring-opening polymerization reaction using cholesterol as initiator. Their structures were confirmed by 1H NMR and FT-IR spectroscopy, and their various dielectric properties were extensively investigated in a frequency range from 100 Hz to 1 MHz under different voltage conditions (0-20 V). The results revealed that all the obtained polymers have focal conic fan shape textures of the smectic phase, encouraging the mesomorphism. In particular, Chol-PCL30 showed superior dielectric performance and exhibited the highest capacitance values and optimal dielectric stability over the measured frequency spectrum. The study showed a non-linear relationship between the chain length of PCL and dielectric properties, with the medium chain length (n = 30) providing the most favorable molecular architecture for enhanced charge capability and dielectric response. Complex impedance analysis revealed a pronounced relaxation behavior as a function of chain length, with Chol-PCL30 showing the most pronounced impedance response. These results provide valuable insights into the structure-property relationships in cholesterol-modified PCL systems and their potential applications in dielectric materials. To address the limitations of existing dielectric materials and explore novel polymeric systems with enhanced electrical properties, cholesterol-functionalized linear poly (epsilon-caprolactone) (Chol-PCL) polymers were successfully synthesized with precisely controlled chain lengths (n = 10, 20, 30, and 70) via ring-opening polymerization using cholesterol as an initiator. Structural confirmation was achieved through 1H NMR and FT-IR spectroscopy. A comprehensive investigation into their dielectric properties, including capacitance, conductance, dielectric constant, dissipation factor, electrical modulus, and impedance, was conducted across a broad frequency range (100 Hz-1 MHz) under varying voltage conditions (0-20 V). All synthesized polymers exhibited focal conic fan shape textures characteristic of the smectic phase, indicating their mesomorphic nature. Notably, Chol-PCL30 demonstrated exceptional dielectric performance, exhibiting the highest capacitance values and notable dielectric stability across the measured frequency spectrum. This study revealed a significant non-linear correlation between the PCL chain length and the observed dielectric properties, with the medium chain length (n = 30) providing an optimal molecular architecture for enhanced charge storage capability and dielectric response. Furthermore, complex impedance analysis elucidated a pronounced relaxation behavior that was highly dependent on chain length, with Chol-PCL30 exhibiting the most significant impedance response. These findings offer crucial insights into the intricate structure-property relationships within cholesterol-modified PCL systems, paving the way for their potential application in advanced dielectric materials.Öğe Comprehensive experimental and computational analysis of endemic Allium tuncelianum: Phytochemical profiling, antimicrobial activity, and In silico studies for potential therapeutic applications(Elsevier Ltd, 2025) Ozdemir, Oguzhan; Yilmaz, Nurten; Musatat, Ahmad Badreddin; Demirci, Tuna; Çete, Servet; Yerlikaya, Emrah; Kaya, Mustafa OğuzhanAllium tuncelianum (TG), an endemic garlic species from Tunceli, Turkey, was investigated using a multidisciplinary approach combining experimental and computational methods. Density Functional Theory (DFT) calculations with B3LYP/def2-SVP/def2-TZVP basis sets were employed to analyze electronic properties, reactivity, and stability under gas and ethanol conditions. Headspace/GC-MS identified 10 major components, with diallyl disulfide (48.03 %) and 1-propene (20.72 %) as predominant. Antimicrobial assays revealed potent activity against MRSA, Salmonella paratyphi A, and E. coli, with MIC values as low as 0.063 mg/mL. Antioxidant capacity, evaluated via DPPH, metal chelating, and FRAP assays, showed promising results, with the water extract exhibiting the highest activity (1.74 mg BHT equivalent/mL). DFT and molecular docking studies highlighted key compounds as potential inhibitors of E. coli Gyrase B, with binding energies of −5.68 and −6.07 kcal/mol. ADME predictions indicated favorable drug-like properties, though some compounds showed potential CYP450 interactions and toxicity. This study provides a comprehensive understanding of TG's biochemical profile and therapeutic potential, offering insights for future research and optimization. © 2025 Elsevier B.V., All rights reserved.Öğe Computational exploration of lichen secondary metabolite usnic acid: electronic properties, ADMET profiling, and antiviral potential against dengue virus NS5 protein(Springer/Plenum Publishers, 2025) Musatat, Ahmad Badreddin; Sevinc, Omer SeyfettinThis study comprehensively evaluates the lichen-derived usnic acid (UA) as a potential antiviral agent targeting the dengue virus NS5 protein. Density functional theory (DFT) employs B3LYP/PBE0 methodologies alongside def2-SVP/TZVP basis sets, revealing UA's electronic profile: moderate HOMO-LUMO gaps (3.80-4.24 eV), high electrophilicity (16.25-20.47 eV), and solvation-induced polarization (dipole moments up to 5.23 Debye). Molecular electrostatic potential (MEP) and reduced density gradient (RDG) analyses identified reactive oxygen sites and intramolecular hydrogen bonding, which are critical for biological interactions. ADMET predictions highlighted favorable drug-like properties (MW = 344.09 g/mol, HIA = 99.12%) but flagged liabilities, including poor solubility (logS = - 4.34), high plasma protein binding (97.16%), hepatotoxicity (DILI probability = 0.991), and CYP-mediated metabolism (CYP2C9/2C19 inhibition > 0.89). Molecular docking demonstrated UA's superior binding affinity (- 8.03 kcal/mol) to NS5 compared to the control ligand, driven by hydrogen bonds with Asp146/Val132 and hydrophobic interactions. However, rapid clearance (t(1)/(2) = 1.45 h) and toxicity risks necessitate structural optimization. This work positions UA as a promising scaffold for antiviral development, contingent on mitigating metabolic instability and toxicity through targeted modifications. The integration of quantum chemical, pharmacokinetic, and docking analyses provides a robust framework for advancing therapeutics derived from UA.Öğe Dielectric property enhancement of glass fiber-reinforced concrete via TiO? nanocomposites(Elsevier, 2025) Ramazanoğlu, Doğu; Subaşı, Azime; Musatat, Ahmad Badreddin; Demir, Ahmet; Subaşı, Serkan; Maraşlı, MuhammedThis study addresses the critical gap in traditional glass fiber-reinforced concrete (GFRC), which lacks tailored electrical properties for modern energy-related applications. We introduce a novel approach by incorporating a TiO?-based hybrid composite (TiO?-@) into GFRC to develop multifunctional composites with enhanced dielectric, mechanical, and energy storage capabilities. Experimental results demonstrate that TiO?-@ doping at 2 % concentration achieves the most significant improvements: a dielectric constant increase to ~420 at 100 Hz (compared to ~180 for undoped GFRC), capacitance enhancement to 71 pF at 100 Hz (versus 18 pF in the reference), and AC conductivity elevation by 205 % after aging. The 2 % TiO?-@ sample also exhibited a Leeb hardness increase to 486 HLD (from 159 HLD pre-aging), highlighting its structural robustness. Frequencydependent analyses revealed modified polarization mechanisms and charge transport dynamics, with ColeCole plots and impedance spectroscopy confirming reduced capacitive reactance and enhanced interfacial interactions. These results establish TiO?-@ as a transformative additive for GFRC, bridging the gap between structural performance and energy functionality. The work pioneers the integration of TiO? nanocomposites into cementitious matrices, offering a dual-purpose material for smart construction systems and embedded energy storage devices.Öğe Employing of 2-Acetylpyridine Based Chalcone as Hg2+ Sensing Material: Experimental and Theoretical Examination(Düzce Üniversitesi, 2022) Musatat, Ahmad Badreddin; Atahan, Alparslan; Aksu, Mecit; Zengin, MustafaThis study reports the evaluation of 2-acetylpyridine based chalcone structure as a useful sensing material for Hg2+ ion detection by the means of UV-visible spectroscopy. In this context, firstly, the most common twenty metal ions were treated by the chalcone structure which was synthesized from 2-acetylpyridine and 4-diphenylaminobenzaldehyde according to the known procedures. As result, the studied chalcone compound exhibited good sensing activity towards Hg2+ ion in acetonitrile/water medium with significant red-shift phenomenon. In addition, some photophysical/electronic parameters of the chalcone and its Hg2+ complex were determined experimentally and theoretically. B3LYP, PBE0 methods and SVP, TVZP, and TVZPP basis sets were used for theoretical calculations in acetonitrile media. Finally, experimental results were explained and the proposed sensing mechanism was supported via density functional theory (DFT) outputs.Öğe Evaluation of Benzothiazole-Chalcone Hybrids: Apoptosis Induction, Docking Analysis, and Anticancer Potential in Gastric Cancer Cells(Springer, 2025) Kiliccioglu, Ilker; Dulger, Gorkem; Musatat, Ahmad Badreddin; Atahan, Alparslan; Caliskan, Emel; Alpay, Merve; Zengin, MustafaThis study investigated a series of chalcone derivatives containing benzothiazole groups (C1-7) for their antimicrobial, antioxidant, and anticancer potential against gastrointestinal cancer cell lines. The compounds showed the highest antiproliferative effect in AGS gastric cancer cells compared to HCT116 colon cancer and HepG2 hepatocellular carcinoma cells. Among the tested compounds, C3 and C4 exhibited the most potent antiproliferative effects (IC50 = 7.55 mu g/mL and 8.25 mu g/mL at 48 h, respectively), significantly outperforming Cisplatin (IC50 = 15.71 mu g/mL). Mechanistic investigations revealed that C3 and C4 induce apoptosis by upregulating caspase-3, -8, and -9, suppressing anti-apoptotic Bcl-2, and elevating pro-apoptotic Bax and p53 proteins. These compounds also impeded AGS cell migration. Antimicrobial evaluations demonstrated an effective profile against multi-drug resistant bacteria, and their effects were comparable to those of the reference antibiotic Ciprofloxacin (< 0.5 g/mL). Antifungal activity results showed that MIC values ranged from < 0.5 to 256 mg/mL. Antioxidant profiling identified C1 as the most potent antioxidant, while C3 exhibited a unique dual role as an oxidant and pro-apoptotic agent. DFT computational studies harmonized the experimental findings, with molecular docking revealing high binding affinities of C3 and C4 to apoptosis regulators Bcl-2 and survivin. ADME predictions affirmed favorable drug-likeness, with moderate solubility, optimal distribution, and synthetic feasibility. This study provides a robust framework for developing benzothiazole-chalcone hybrids as precision therapeutics, positioning C3 and C4 as promising candidates for gastric cancer therapy.Öğe Evaluation of Industrial Poly(tert-butyl acrylate) insulated A p-channel Organic Field-Effect Transistor (PtBA-p-OFET)(Duzce University, 2024) Demir, Ahmet; Musatat, Ahmad BadreddinPoly(tert-butyl acrylate) (PTB-p-A) has been investigated as a promising insulator layer for p-channel organic field effect transistors (p-OFETs) using the p-type semiconductor Poly(3-hexylthiophene-2,5-diyl (P3HT) due to its favorable insulating properties, good film-forming ability and electrical charge separation properties. Top-gate, bottom-contact PTBA-p-OFET devices are fabricated with Indium Thin Oxide (ITO) source/drain electrodes and a P3HT organic semiconductor layer. The frequency-dependent capacitance of the PTBA-p-OFETs was studied through a plot to determine the key parameters, including the threshold voltage (VTh), field-effect mobility (µFET), and the current on/off ratio (Ion/off) of the device. The PTB-p- OFETs exhibit field-effect mobility value of 6.13x10-4 (cm2/V.s), an on/off current ratio of 1.11x102, and a threshold voltage of -15.8 V. The capacitance-frequency characteristics of the capacitor structure were analyzed and found to have as 7.6 nF/cm2 per unit area. This work presents PTBA as a promising for high-performance p-OFET applications.Öğe Harnessing high potential benzothiazole chalcones against dengue virus NS5 protein: A multi-faceted theoretical study through molecular docking, ADME, and DFT(Elsevier Science Inc, 2024) Musatat, Ahmad Badreddin; Durmus, Tulay; Atahan, AlparslanChalcones bearing tetralone, indanone and benzothiazole cores were synthesized successfully using a general Claisen-Schmidt condensation protocol. The prepared compounds were purified and structurally analyzed by 1H, 13C NMR, and FT-IR techniques. A multi-faceted theoretical approach, combining Density Functional Theory (DFT), molecular docking, and ADME predictions, was employed to evaluate their therapeutic potential. DFT calculations at the B3LYP/def2-TZVP level revealed key electronic properties, with TD3 compound demonstrating the highest chemical reactivity. Molecular Electrostatic Potential (MEP) and Reduced Density Gradient (RDG) analyses provided insights into the compounds' non-covalent interactions and charge distributions. Molecular docking studies against the NS5 protein (PDB: 6KR2) showed superior binding affinities for all three compounds compared to the control ligand SAH, with TD3 exhibiting the lowest binding energy (-8.41 kcal/ mol) and theoretical inhibition constant (689.31 nM). ADME predictions indicated favorable drug-like properties with concerns regarding aqueous solubility and potential P-glycoprotein interactions. Toxicity evaluations highlighted challenges, particularly in hepatotoxicity and carcinogenicity. The study identified TD3 as a promising lead compound for Dengue Virus NS5 inhibition, while also emphasizing the need for targeted modifications to address toxicity concerns. This research not only contributes to anti-dengue drug discovery efforts but also provides a robust methodological framework for the theoretical evaluation of similar small compounds in future investigations.Öğe In silico investigation of tetrazole and oxadiazole compounds as inhibitors of the dengue virus NS5 protein: Synthesis, DFT, ADME and molecular docking analysis(Elsevier Ireland Ltd, 2025) Demirci, Tuna; Musatat, Ahmad Badreddin; Kaya, Mustafa Oguzhan; Arslan, MustafaThis study investigates the therapeutic potential of novel tetrazole and oxadiazole derivatives targeting the Dengue virus NS5 protein through an integrated computational and experimental approach. A series of nitrilesubstituted 1,4-dihydropyridine (1,4DHPs) derivatives were synthesized and converted into tetrazole and 1,3,4-oxadiazole analogs using established protocols. Structural characterization was performed via NMR, FT-IR, and elemental analysis. Molecular docking studies against the NS5 protein (PDB ID: 6KR2) revealed superior binding affinities for several compounds (Delta G = -7.18 to -9.58 kcal/mol), with compound 5 exhibiting the strongest interaction (Delta G = -9.58 kcal/mol, theoretical IC50 = 94.64 nM), outperforming the reference ligand SAH (Delta G = -7.18 kcal/mol). ADME profiling demonstrated favorable drug-likeness, acceptable solubility, bloodbrain barrier penetration, and CYP450 metabolic stability. DFT analyses elucidated electronic properties, including HOMO-LUMO gaps (2.72-4.80 eV) and electrophilicity indices (13.5-23.6 eV), correlating with observed bioactivity. Toxicity predictions identified compound-specific liabilities requiring optimization. These findings highlight the promise of tetrazole-oxadiazole hybrids as potent NS5 inhibitors, warranting further preclinical validation for Dengue therapeutic development.Öğe Multifunctional GFRC composites: PEDOT: PSS-driven dielectric enhancement for energy storage and sensing applications(Elsevier Science Sa, 2026) Demir, Ahmet; Musatat, Ahmad Badreddin; Subasi, Azime; Ramazanoglu, Dogu; Dehgan, Haydar; Marasli, Muhammed; Gencel, OsmanThis study presents a comprehensive investigation into the development and characterization of multifunctional Glass Fiber Reinforced Cement (GFRC) composites enhanced with Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT: PSS) to impart advanced electrical properties. We systematically analyzed the influence of PEDOT: PSS concentration (0-15 wt %) and curing age on the dielectric behavior of these novel composites, evaluating their capacitance, dielectric constant, loss factor, and electrical modulus across a broad frequency range (10 Hz-10 MHz). The integration of PEDOT: PSS significantly modified the material's electrical characteristics, demonstrating concentration-dependent variations and complex relaxation mechanisms dominated by Maxwell-Wagner interfacial polarization. The optimized P2 formulation (10 wt % PEDOT: PSS) exhibited superior electrochemical performance, maintaining the highest capacitance values and achieving a peak dissipation factor (tan delta) of 0.43 +/- 0.02 at day 15, representing a 185 % enhancement over unmodified GFRC. EDX analysis confirmed successful polymer incorporation, with P2 exhibiting the highest carbon content (5.8 wt %) and sulfur content (1.8 wt %), indicating optimal dispersion. Equivalent circuit models were established and validated (R2 > 0.98), providing insights into complex charge transport mechanisms within this hybrid material. Microstructural analyses via scanning electron microscopy revealed significant morphological modifications, including the formation of crystalline and plate-like structures, while complementary FT-IR and TGA analyses confirmed polymer-cement interaction stability and thermal stability up to 450 degrees C. These findings establish fundamental design principles for creating electrically conductive cementitious materials with tunable dielectric properties, enabling strategic deployment in innovative infrastructure systems, energy storage devices, and electromagnetic shielding technologies.Öğe Multifunctional SnO2-@ doped glass fiber?reinforced concrete: Improved microstructure, mechanical, dielectric, and energy storage characteristics(Elsevier, 2025) Ramazanoğlu, Doğu; Subaşı, Azime; Musatat, Ahmad Badreddin; Demir, Ahmet; Subaşı, Serkan; Maraşlı, MuhammedThis study explores SnO?-based hybrid composite (SnO?-@) doped glass fiber-reinforced concrete (GFRC) for enhanced dielectric, energy storage, and mechanical performance. Microstructural analysis confirmed SnO?-@ promotes ettringite and calcium silicate hydrate (C-S-H) formation, improving matrix integrity. Aged samples exhibited a 650?% increase in surface roughness (Ra) and over 200?% higher Leeb hardness, demonstrating durability. Dielectric spectroscopy revealed frequency-dependent tunability: 1?% SnO?-@ achieved a peak dielectric constant (?' = 130 at 10?kHz), shifting to ?' =?140 at 100?kHz for 2–3?% doping. AC conductivity surged by 60?%, correlating with SnO?-@-induced interfacial polarization and charge mobility. Energy storage capacity improved significantly, attributed to optimized dipole alignment and reduced leakage currents. Color stability remained robust (?E* ? 2.8 post-aging), ensuring aesthetic viability. These results position SnO?-@-doped GFRC as a multifunctional material for smart infrastructure, integrating structural resilience, adaptive dielectric properties, and energy storage potential for next-generation urban applications.Öğe Novel eco-friendly approach employing recycled waste ferrochrome slag in cellulose-based bioconductive paper production: Energy harvesting and electro-optical properties(Elsevier, 2025) Gencel, Osman; Musatat, Ahmad Badreddin; Demir, Ahmet; Tutus, Ahmet; Tozluoglu, Ayhan; Cavus, Fatma KosovaliThis pioneering research incorporates ferrochrome slag (FS), a byproduct of metal extraction, with recycled pulp paper to improve electrical conductivity in an environmentally acceptable manner. The alternating current (AC) electrical conductivity exhibited consistent behavior from 100 Hz to 5 MHz at room temperature. A remarkable twofold increase in conductivity was achieved by elevating the FS ratio from 20 % to 25 % in the direct current region. Distinct trends were evident in 's' values, which serve as a measure of the level of interaction between mobile ions and their surroundings across frequency segments. The AF-Region (100 Hz - 2 kHz) yielded 's' values of 0.627-0.640, preferring values below 1, while the LRF-Region (2 kHz - 90 kHz) yielded values of 1.74-1.77, preferring values above 1. The sample with FS 25 % showed heightened conductive potential. Capacitance values and real permittivity (epsilon') increased noticeably at 100 Hz and 1 kHz with higher FS doping rates. By evaluating physical, optical, mechanical, electrical, and morphological properties, this study reveals the latent potential of FS integration, advancing electrical conductivity through an eco-friendly approach. This unique waste valorization underscores FS as a game-changing material for paper production leading to further environmental perspectives.Öğe Phytochemical profiling, anticancer effects on hepatocellular carcinoma and antimicrobial activities of four edible fungi: Unraveling mechanisms by molecular docking studies(Elsevier, 2025) Kurman, Yener; Dulger, Gorkem; Nazli, Hakan; Gedik, Gulsah; Dulger, Basaran; Musatat, Ahmad BadreddinEdible mushrooms, with their nutritional composition, pleasant taste, and flavor, have been used in food and traditional medicine worldwide for many years. Due to their secondary metabolites, they exhibit broad biological activities. This research aimed to analyze the phenolic contents by Liquid chromatography-mass spectrometry (LC/MS) and investigate the anticancer and antimicrobial properties of Cantharellus cibarius, Craterellus cornucopioides, Ramaria formosa, and Hydnum repandum extracts. The antimicrobial and antioxidant activity of extracts was determined by the well diffusion method and colorimetric assay kit, respectively. The extracts' ability to inhibit cell proliferation was tested on hepatocellular carcinoma (HCC) cell line HepG2 and Human umbilical vein endothelial cells (HUVECs) using the WST-1 (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2Htetrazolium, monosodium salt) assay. The effect of H. repandum extract on the levels of Bcl-2-Associated X (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3, cyclin D1, and p53 proteins' expression was assessed through the western blot, and its influence on apoptosis was investigated using flow cytometry. Antimicrobial activity results revealed that the extracts produced inhibition zones ranging from 9.8 to 16.8 mm against bacteria and 9.8-17.6 mm against yeasts. H. repandum showed high antibacterial and antioxidant (7.45 +/- 0.17 mmol Trolox equivalent/L) activities attributable to its high chlorogenic and gallic acid content. H. repandum also showed the highest selective cytotoxicity against HepG2 cells compared to control HUVECs. H. repandum extract triggered apoptosis in HepG2 cells, markedly elevated the expression of Bax, p53, and caspase-3, and substantially reduced the levels of cyclin D1. Binding interactions between caspase-3 and the most abundant compounds in the H. repandum extract, alongside their pharmacokinetic profile, were supported by molecular docking analysis and absorption, distribution, metabolism, and excretion (ADME) studies.Öğe Rabbit muscle pyruvate kinase activators: Synthesis, molecular docking and theoretical studies of N-substituted sulfonamide derivatives(Elsevier, 2024) Kaya, Mustafa Oguzhan; Demirci, Tuna; Musatat, Ahmad Badreddin; Ozdemir, Oguzhan; Sonmez, Fatih; Kaya, Yesim; Arslan, MustafaPyruvate kinase (PK) activators have potential therapeutic applications in diseases such as sickle cell anemia. In this study, N-Substituted sulfonamide derivatives of 1,4-dihydropyridines were synthesized and evaluated as PK activators in vitro and using molecular docking studies. The compounds were synthesized by reacting dicarbonyl compounds with ammonium acetate, 5-nitrobenzaldehyde, and alumina sulfuric acid (ASA), followed by reduction and sulfonylation. The structures of the compounds were analyzed using spectroscopic techniques. DFT calculations provided insights into the electronic properties. Molecular docking of the compounds into the active site of PK showed favorable binding interactions. ADME evaluation indicated suitable solubility, BBB permeation, and lack of CYP450 inhibition. Overall, this study demonstrates the potential of new hybrid 1,4-dihydropyridine substituted sulfonamides as PK activators for further development. According to AC50 values, the compound (DTS-F-7, 0.97 mu M) is about 100-fold higher affective than the clinically used sulfonamide compound (AC50 = 90 mu M) for PK.Öğe Rational design, biological and in-silico evaluation of quinoline-chalcone hybrids: A new series of antimicrobial and anticancer agents(Elsevier Ltd, 2026) Kiliçcioğlu, Ilker; Musatat, Ahmad Badreddin; Dülger, Görkem; Atahan, Alparslan; Dülger, Başaran; Zengin, MustafaThis study investigates the synthesis, antimicrobial, anticancer, and in silico properties of novel quinoline-chalcone hybrids (nQCa-l), which were synthesized and characterized. Their antimicrobial activity revealed broad-spectrum efficacy, with compound 2QC-h demonstrating superior potency compared to several standard antibiotics and antifungals. The anticancer potential was assessed against gastrointestinal system cancer cell lines (AGS, HepG2, HCT116), where 2QC-h emerged as the most potent antiproliferative agent, often surpassing oxaliplatin in efficacy, particularly in AGS gastric cancer cells. Mechanistic studies have demonstrated that 2QC-h synergistically induces apoptosis and inhibits epithelial-mesenchymal transition (EMT) in AGS cells through the intrinsic mitochondrial pathway, thereby enhancing the anticancer effect of oxaliplatin. Crucially, 2QC-h exhibited selective cytotoxicity towards gastrointestinal system cancer cells (AGS cells: 4.85 ± 0.22 µg/mL and 2.66 ± 0.58 µg/mL, HCT116 cells: 6.61 ± 0.29 µg/mL and 2.39 ± 0.57 µg/mL, and HepG2 cells: 9.14 ± 0.49 µg/mL and 6.15 ± 0.27 µg/mL for 24 h and 48 h, respectively) and minimal morphological effects on healthy HUVEC cells. Computational studies, including DFT analysis, MEP, RDG, ELF, LOL, and ALIE, provided comprehensive insights into the electronic structure, reactivity, and non-covalent interactions, elucidating the structure-activity relationships (SAR). Molecular docking simulations identified VEGFR-2 and EGFR as the preferential targets for these derivatives, with nanomolar binding affinities, which correlated strongly with experimental cytotoxic potencies. ADME highlighted favorable drug-likeness properties while identifying areas for further optimization. Overall, this research establishes quinoline-chalcone hybrids as promising multi-target therapeutic agents with significant potential for developing novel antimicrobial and anticancer drugs. © 2025 Elsevier B.V., All rights reserved.Öğe Rational Design, Synthesis, and Computational Investigation of Dihydropyridine [2,3-d] Pyrimidines as Polyphenol Oxidase Inhibitors with Improved Potency(Springer, 2024) Kaya, Mustafa Oguzhan; Kerimak-Oner, Mine Nazan; Demirci, Tuna; Musatat, Ahmad Badreddin; Ozdemir, Oguzhan; Kaya, Yesim; Arslan, MustafaPolyphenol oxidase (PPO) is an industrially important enzyme associated with browning reactions. In the present study, a set of ten new dihydropyridine [2,3-d] pyrimidines (TD-Hid-1-10) were synthesized and was found to be proven characteristically by 1H NMR, 13C NMR, IR, elemental analysis, and assessed as possible PPO inhibitors. PPO was purified from banana using three-phase partitioning, achieving an 18.65-fold purification and 136.47% activity recovery. Enzyme kinetics revealed that the compounds TD-Hid-6 and TD-Hid-7 are to be the most potent inhibitors, exhibiting mixed-type inhibition profile with IC50 values of 1.14 mu M, 5.29 mu M respectively against purified PPO enzyme. Electronic structure calculations at the B3LYP/PBE0 level of theories using def-2 SVP, def2-TZVP basis sets with various molecular descriptors characterized the electronic behavior of studied derivatives TD-Hid-1-10. Molecular electrostatic potential (MEP) and reduced density gradient analyses of RDG-NCI provided insights into charge distributions and weak intermolecular interactions. Docking study simulations predicted binding poses within crucial amino acid sequence in the 2y9x enzyme's active site, which is typically similar in sequence to the PPO form is not allowed. Ligands were analysed in terms of binding energies, inhibitor concentrations (mM) and various molecular interactions such as H-bonds, H-carbon, pi-carbon, pi-sigma, pi-sigma, pi-pi T-shaped, pi-pi stacked, pi-alkyl, Van der Waals and Cu interactions. The lowest binding energy (-7.83 kcal/mol) and the highest inhibitory effect (1.83 mM) were shown by the ligand Td-Hid-6, which forms H-bonds with Met280 and Asn260, exhibits pi-sigma interactions with His61 and pi-alkyl interactions with Val283. Other ligands also showed different interactions with various amino acids; for example, the Td-Hid-1 ligand formed H-bonds with His244 and showed pi-sigma interactions with His244 and Val283.Öğe Siringaldehit Bazlı Yeni 2,4,6-Triarilpiridin Türevlerinin Antioksidan Aktiviteleri ve Teorik Profili(Duzce University, 2024) Albayrak, Esra Nur; Şimşek, Samed; Musatat, Ahmad Badreddin; Akşit, Zeynep; Akşit, Hüseyin; Atahan, AlparslanSiringaldehitten türetilen sekiz adet yeni 2,4,6-triarilpiridin tasarlandı ve tek basamaklı multi-komponent yöntemle sentezlendi. Bu bileşiklerin antioksidan aktiviteleri bilinen referans bileşiklerle kıyaslanarak değerlendirildi. Daha sonra, B3LYP teorisi ve SVP, TVZP temel setleri kullanılarak, sentezlenen bileşikler için kapsamlı bir teorik kuantum hesaplama yaklaşımı oluşturuldu ve radikal yakalama potansiyelini tanımlayan Fukui indeksleri adlı elektronik yapı tanımlayıcı parametreler belirlendi. Son olarak, teorik ve deneysel sonuçlar karşılaştırılarak yapı-etkinlik ilişkisi ortaya konuldu. Sonuç olarak, elde edilen bileşiklerin antioksidan aktivite potansiyeli teorik bir yaklaşımla da desteklendi.Öğe Synergistic fusion of carbazole, quinoline, and chalcone scaffolds: A computational and experimental exploration of hybrid compounds as selective anticancer agents(Elsevier, 2025) Musatat, Ahmad Badreddin; Kiliccioglu, Ilker; Louaileche, Tinhinane; Dulger, Gorkem; Maouche, Chaima; Tabti, Salima; Kurman, YenerNovel carbazole-quinoline-chalcone hybrids (nQCC1-4) were synthesized via Claisen-Schmidt condensation and evaluated against AGS gastric adenocarcinoma cells. The most potent compound, 1QCC-1, exhibited significant antiproliferative activity (IC50 values of 19.11 mu g/mL and 7.91 mu g/mL at 24 h and 48 h). Compounds 1QCC-4, 1QCC-3, and 2QCC-2 demonstrated comparable cytotoxic efficacy against AGS cells. Density functional theory (DFT) calculations revealed substituent-dependent electronic properties, with chloro-quinoline derivatives displaying enhanced electrophilicity (omega = 13.745-14.157 eV) and reduced HOMO-LUMO gaps (Delta E = 3.304-3.347 eV), correlating with improved bioactivity profiles. Molecular docking studies identified robust binding interactions with oncogenic targets, MAPK1 p38 kinase, HER2, and RhoA, with 1QCC-4 exhibiting superior binding affinity for HER2 (Delta G = -12.05 kcal/mol, IC50 = 1.48 nM) through hydrogen bonding with Lys114 and it-alkyl interactions with Leu156. ADMET profiling highlighted favorable drug-likeness parameters despite solubility challenges (LogS = -7.846 to -6.291) and potential CYP450 inhibition. Non-covalent interaction (NCI-RDG) and molecular electrostatic potential (MEP) analyses elucidated key stabilizing interactions and nucleophilic/electrophilic hotspots. These hybrids represent a strategic integration of natural product pharmacophores, leveraging synergistic electronic and steric effects for selective kinase inhibition, positioning them as promising leads for targeted gastric cancer therapy.Öğe Synthesis and Evaluation of 1,4-Dihydropyridine-Based Urea Derivatives as Polyphenol Oxidase Inhibitors(Siirt Üniversitesi, 2024) Kaya, Mustafa Oğuzhan; Demirci, Tuna; Taş, Halil İbrahim; Karayağız, Şeyda; Musatat, Ahmad Badreddin; Kaya, Yeşim; Öner, Mine Nazan KerimakThis study investigated the potential inhibitory effects of nine novel synthesized urea-substituted 1,4-dihydropyridine derivatives (DT-DEN-1-9) on polyphenol oxidase (PPO) activity. The compounds were synthesized via the Hantzsch reaction, providing a series of structurally diverse urea and thiourea-modified 1,4-dihydropyridines. Polyphenol oxidase enzyme was extracted from banana (Musa cavendishii) and purified using affinity chromatography with a Sepharose 4B-L-tyrosine-p-aminobenzoic acid affinity gel. The purified enzyme's activity was measured spectrophotometrically using catechol as the substrate, monitoring the increase in absorbance at 420 nm. The inhibitory effects of the synthesized compounds on PPO activity were evaluated through in vitro assays. Various concentrations of each compound were incorporated into the enzyme reaction mixture, and the residual PPO activity was determined. The percentage of PPO activity was calculated relative to a control reaction without inhibitors. IC50 values, representing the concentration of inhibitor required to reduce enzyme activity by 50%, were determined using Lineweaver-Burk plots. Among the tested compounds, DT-DEN-6, featuring a phenyl thiourea substituent, exhibited the most potent inhibition with an IC50 value of 100.14 µM. DT-DEN-8, containing a 2,5-dichlorophenyl thiourea moiety, also showed strong inhibitory activity with an IC50 below 150 µM. Structure-activity relationships were observed, with electron-withdrawing substituents generally enhancing inhibitory potency. Conversely, DT-DEN-5, bearing a 4-(trifluoromethyl)phenyl thiourea substituent, exhibited the weakest inhibition profile (IC50: 233.33 µM). Our findings provide valuable insights for the design of next-generation PPO inhibitors, potentially leading to the development of novel anti-browning agents for applications in food preservation and other industries where control of enzymatic browning is crucial.
