Browsing by Author "Karaman, Muhammet"

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Inhibition Effects of Isoproterenol, Chlorpromazine, Carbamazepine, Tamoxifen Drugs on Glutathione S-Transferase, Cholinesterases Enzymes and Molecular Docking Studies
(Taylor & Francis inc, 2021) Turkan, Fikret; Calimli, Mehmet Harbi; Kanberoglu, Gulsah Saydan; Karaman, Muhammet
Nowadays, inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and glutathione S-transferases (GSTs) have been a very crucial issue for pharmacological treatments of several disasters. Herein, we investigated inhibition effects of Tamoxifen (TAM), Isoprenaline (ISO), Chlorpromazines (CPZ) and Carbamazepine (CBZ) on GST, AChE, BChE and then molecular structures and active sides of the tested drugs by molecular docking process. The enzyme activity results showed that nearly the whole tested drugs inhibited GST, BChE, AChE efficiently. Chlorpromazine was found to be the best inhibitor for the GST enzyme and the Ki value of this drug was found to be 42.83 +/- 8.52 nM. Besides, Isoproterenol drug with the Ki value of 51.80 +/- 9.44 nM was found to be the most effective inhibitor on the AChE enzyme. Molecular docking studies showed that the receptor-binding sites of GST, AChE, and BChE were found to 1.069, 1.090, and 1.15 of Sitecore and 0.992, 1.113, and 1.217 of Dscore, respectively. The method was validated by doing validation studies and these validations revealed that re-docked ligands located a very closed position with co-crystallized ligand into the active site for all receptors. Calculation studies for determining the possible enzyme inhibition mechanism with the used drugs revealed that amino and aromatic ring in the structure of the drugs used are effective in inhibition reactions. Communicated by Ramaswamy H. Sarma
Pyrazole[3,4-D]pyridazine Derivatives: Molecular Docking and Explore of Acetylcholinesterase and Carbonic Anhydrase Enzymes Inhibitors as Anticholinergics Potentials
(Academic Press inc Elsevier Science, 2019) Taslimi, Parham; Turkan, Fikret; Cetin, Adnan; Burhan, Hakan; Karaman, Muhammet; Bildirici, Ishak; Sen, Fatih
Recently, the pyridazine nucleus has been widely studied in the field of particular and new medicinal factors as drugs acting on the cardiovascular system. Additionally, a number of thienopyridazines have been claimed to possess interacting biological macromolecules and pharmacological activities such as NAD(P)H oxidase inhibitor, anticancer, and identified as a novel allosteric modulator of the adenosine A1 receptor. The literature survey demonstrates that coumarin, 1,2-pyrazole benzothiazole, and 1,3- thiazole scaffolds are the most versatile class of molecules. In this study, a series of substituted pyrazole[3,4-d]pyridazine derivatives (2a-n) were prepared, and their structures were characterized by Mass analysis, NMR, and FT-IR. These obtained pyrazole [3,4-d]pyridazine compounds were very good inhibitors of the carbonic anhydrase (hCA I and II) isoenzymes and acetylcholinesterase (AChE) with K-i values in the range of 9.03 +/- 3.81-55.42 +/- 14.77 nM for hCA I, 18.04 +/- 4.55-66.24 +/- 19.21 nM for hCA II, and 394.77 +/- 68.13-952.93 +/- 182.72 nM for AChE, respectively. The possible inhibition mechanism of the best-posed pyrazole[3,4-d]pyridazine and pyrazole-3-carboxylic acid derivatives and their interaction with catalytic active pocket residues were determined based on the calculations.