Browsing by Author "Cetin, A."

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Antiproliferative Effects of Pyranopyrazole Analogs: In Vitro and Molecular Docking Analysis
(KeAi Communications Co., 2026) Nalci, K.A.; Cetin, A.; Bildirici, I.; Bayram, U.F.
Background Glioblastoma multiforme is the most aggressive primary brain tumor in adults, and current multimodal therapies provide only limited survival benefit. There is an urgent need for new small-molecule scaffolds with improved anticancer activity against glioblastoma. Objective To evaluate the antiproliferative effects of pyranopyrazole analogs on human U-87 MG glioblastoma cells and to explore their potential molecular interactions with a glioblastoma-related protein target by molecular docking. Methods A series of pyranopyrazole analogs ( 12a – o ) was synthesized using a previously reported green-chemistry protocol. U-87 MG cells were treated with increasing concentrations of the analogs for 24, 48, and 72 h, and cell viability was measured by a colorimetric tetrazolium-based assay. Half-maximal inhibitory concentration values were determined for the most active analogs and compared with those of a reference chemotherapeutic agent. Molecular docking was performed with the 6c1c protein structure to assess binding energies and interaction profiles. Results Several pyranopyrazole analogs produced dose- and time-dependent cytotoxicity in U-87 MG cells. Analog 12 g showed the strongest antiproliferative effect and lower half-maximal inhibitory concentration values than the reference agent at earlier time points, whereas 12 h , 12o , and 12i displayed moderate activity. Docking analysis indicated favorable binding of active analogs to the 6c1c active site, with multiple hydrogen-bond and π-type interactions involving key residues. Conclusion Pyranopyrazole analogs, particularly 12 g , exhibit promising antiproliferative activity against glioblastoma cells in vitro, supported by compatible molecular docking findings. These compounds may represent useful lead structures for the development of new chemotherapeutic options for glioblastoma. © 2026 The Authors.
Design, Synthesis, and AChE Inhibition of 4-Amino Derivatives: Molecular Docking and Biological Evaluation
(Pleiades Publishing Ltd, 2025) Oguz, E.; Cetin, A.; Kazancioglu, M. Z.; Kazancioglu, E. A.; Turkan, F.
Substituted tetrahydroquinoline (THQ) derivatives were systematically designed and synthesized via a three-component Povarov reaction, employing N-vinyl carbamate, organocatalyzed substituted anilines, and benzaldehyde derivatives. The resulting THQ derivatives demonstrated a diverse range of functional groups, which potentially broadens their applicability. These compounds were rigorously characterized using various spectroscopic techniques to verify their structures. Subsequent bioevaluation of the synthesized THQs revealed their inhibitory activity against acetylcholinesterase (AChE), highlighting their potential as therapeutic agents for neurodegenerative diseases. All synthesized THQs exhibited IC50 values ranging from 0.22 to 0.36 mu M, which are lower than the IC50 value of the standard compound tacrine (0.77 mu M). The Ki values for the THQs against AChE ranged from 0.370 +/- 0.330 to 1.30 +/- 0.715 mu M. Additionally, molecular docking studies of the THQ-AChE complexes yielded binding scores between -10.8 and -12.4 kcal/mol. The structure-activity relationship (SAR) analysis underscores the significance of THQ structures in medicinal chemistry. These findings suggest that the structural insights gained from this study will be valuable for the future design and synthesis of potent AChE inhibitors.
In Silico and In Vitro Analysis of Acetylcholinesterase and Glutathione S-Transferase Enzymes of Substituted Pyrazoles
(Maik Nauka/interperiodica/springer, 2022) Cetin, A.; Oguz, E.; Tuerkan, F.
A series of substitute pyrazole compounds including azide, acetyl, triazole, morpholine, piperidine, and pyrrolidine moieties were synthesized and their structures were elucidated by NMR, HPLC and mass spectroscopy. The inhibition efficiencies of all novel compounds against acetylcholinesterase (AChE) and glutathione S-transferase (GST) enzymes were investigated. In vitro studies revealed that the inhibitory activities of substitute pyrazole compounds were determined with Ki values in the range of 0.11-0.49 mu M for AChE, and 0.12-0.91 mu M for GST, respectively. Furthermore, the molecular docking studies of the detailed interactions between the pyrazole compounds and AChE-GST enzymes were identified with bonding type, distance, hydrophobic bonds and hydrogen bonds. The binding energies of the AChE-pyrazole analogs' complexes were found between -5.5 and - 9.3 kcal/mol, and the binding energies of the GST-pyrazole analogs' complexes were found between -5.9 and - 9.2 kcal/mol.
Molecular Docking and Pharmacokinetic Studies of Aquillochin and Grewin as Sars-Cov Mpro Inhibitors
(Bentham Science Publishers, 2022) Cetin, A.
Background: The COVID-19 pandemic emerged at the end of 2019 in China and spread rapidly all over the world. Scientists strive to find virus-specific antivirals against COVID-19 disease. This study aimed to assess bioactive coumarinolignans (Aquillochin, Grewin) as potential SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors using a molecular docking study. Methods: The detailed interactions between coumarinolignans and SARS-CoV-2 Mpro were determined as hydrophobic bonds, hydrogen bonds, electronic bonds, inhibition activity, ligand efficiency, bonding type, and distance using Autodock 4.2 software. SARS-CoV-2 Mpro was docked with Aquillochin and Grewin, and the docking results were analyzed by Autodock 4.2 and Biovia Discovery Studio 4.5. Nelfinavir and Lopinavir were used as standards for comparison. Results: The binding energies of the SARS-CoV-2 Mpro-coumarinolignan’s complexes were identified from the molecular docking of SARS-CoV-2 Mpro. Aquillochin and Grewin were found to be-7.5 and-8.4 kcal/mol, respectively. The binding sites of the coumarinolignans to SARS-CoV-2 Mpro were identified with the main interactions being π-alkyl, alkyl, π-cation, π-π T-Shaped, and hydrogen bonding. Furthermore, SwissADME web tools were used to evaluate ADMET properties and pharmacokinetic parameters of Aquillochin and Grewin. The results of ADMET and pharmacokinetic results of the Aquillochin and Grewin showed that these coumarinolignans were consonant with the many accepted rules and the criteria of drug-likeness. Conclusion: Aquillochin and Grewin obey Lipinski’s rule of five. According to the results obtained from molecular docking studies and ADMET predictions, Aquillochin and Grewin have shown weak efficacy as drug candidates against COVID-19 disease. © 2022 Bentham Science Publishers.
Substituted Bipyridine-Based Compounds: Synthesis, Enzyme Inhibition, Anticancer Activities and Molecular Docking Studies
(KeAi Communications Co., 2026) Cetin, A.; Turkan, F.; Oğuz, E.; Rozbicki, P.; Wolinska, E.; Branowska, D.
Background Substituted bipyridine-based compounds with diverse pharmacological activities like anticancer, anti-inflammatory, antimicrobial, antiviral, and antioxidant hold a significant scaffold in the pharmaceutical industry because of their biological activities. Objective These derivatives were synthesized and tested for their inhibitory and cytotoxicity activity against acetylcholinesterase (AChE), glutathione S-transferase (GST), and hepatocellular carcinoma (HepG2). Methods In AChE and GST inhibition measurement methods, a method based on quantitatively evaluating the inhibitory effect by measuring the enzyme's conversion of the substrate into a product and the resulting color change or absorbance of this product has been used. Results These bipyridine-based compounds were found to inhibit these enzymes with IC50 values ranging from 1.99 to 3.15 μM for AChE and from 2.07 to 4.15 μM for GST. The bipyridine-based compounds were tested in a range of 12.5–100 µM concentrations against the HepG2 cell line. Among these derivatives studied, 15c was the most effective substance on HepG2 cells. Conclusion 15c was detected and found to be the best active bipyridine-based compound with an IC50 of 1.99 µM for AChE and 2.07 µM for GST, respectively. Also, 15a and 15d were good inhibitors for both enzymes. The time- and dose-dependent cytotoxicity determined supports bipyridine-based compounds’ potential as chemotherapeutic candidates for HepG2 cells. 15d and 15e derivatives possess good anticancer activity. Furthermore, the molecular docking results indicated that the bipyridine-based compounds predicted strong binding and stability at the active site of enzymes and the cancer line. The bipyridine-based compounds may enable the development of more selective and effective structures as enzyme inhibitors and anticancer drugs in the future. © 2026 The Authors.
Synthesis, Biological Evaluation, and Bioinformatics Analysis of Indole Analogs on Ache and Gst Activities
(Springer, 2022) Cetin, A.; Toptas, M.; Türkan, F.
In this article, we aimed to (1) synthesize novel 3-substitue 2-methyl indole analogs, and (2) evaluate their biological activities against Acetylcholinesterase enzyme (AChE) and Glutathione S-transferase enzyme (GST), (3) predict ADMET and pharmacokinetic properties of the 3-substitue 2-methyl indole analogs (4) reveal the possible interactions between 3-substitue 2-methyl indole analogs and selected enzymes. In vitro enzyme inhibition studies revealed the 3-substitue 2-methyl indole analogs exhibited moderate to good inhibitory activities against AChE and GST enzymes. 2-azido-1-(2-methyl-1H-indol-3-yl)ethanone synthesized was a good inhibitor with the lowest Ki value for both enzymes. Furthermore, a molecular docking study of 3-substitue 2-methyl indole analogs was carried out in the active site of AChE/GST to gain insight into the interaction modes of the synthesized analogs and rationalized structure-activity relationship. The binding energies of the AChE-3-substitue 2-methyl indole analogs’ complexes were found between −9.3 and −6.0 kcal/mol, and the binding energies of the GST-3-substitue 2-methyl indole analogs’ complexes were also found between −11.1 and −7.5 kcal/mol. [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Trisubstituted Imidazole and N-Propargyl Imidazole Analogues: Synthesis, Characterization, in Silico Studies and Enzyme Inhibitory Properties
(Maik Nauka/interperiodica/springer, 2023) Altiok, M. S.; Cetin, A.; Kuzu, B.; Bildirici, I.
In recent years, the alpha-amylase, pancreatic lipase (PL), and beta-glucuronidase enzymes have received much attention as they promise to be potential drug targets for obesity and diabetes-related diseases. In this study, the synthesis and characterization of newly designed tricyclic imidazopyrrolopyrazine analogues with the potential to affect these enzymes were evaluated. The pharmacological evaluation of all imidazopyrrolopyrazine analogues revealed that all the synthesized analogues displayed excellent inhibitory effects against alpha-amylase, with the IC50 values of these analogues ranging from 4.05 +/- 0.7 to 5.61 +/- 0.8 mu M. The IC50 values of all synthesized analogues were also found to be effective inhibitors, ranging from 5.2 +/- 0.5 to 13.7 +/- 2.3 mu M, against pancreatic lipase. Furthermore, all analogues exhibited moderate inhibition in a wide range of 151.4 +/- 9.1 to 302.5 +/- 7.9 mu M against beta-glucuronidase. Additionally, all the synthesized analogues displayed moderate binding affinity with Ferric Reducing Antioxidant Power (FRAP), and low binding affinity with Oxygen Radical Absorbance Capacity (ORAC). This study provides valuable potential for the new tricyclic imidazopyrrolopyrazine analogues in further pharmacological studies.