Browsing by Author "Cetin, A."

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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.
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.