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Öğe Acetylphenyl-substituted imidazolium salts: synthesis, characterization, in silico studies and inhibitory properties against some metabolic enzymes(Springer, 2023) Demirci, Ozlem; Tezcan, Burcu; Demir, Yeliz; Taskin-Tok, Tugba; Gok, Yetkin; Aktas, Aydin; Guzel, BilgehanHerein, we present how to synthesize thirteen new 1-(4-acetylphenyl)-3-alkylimidazolium salts by reacting 4-(1-H-imidazol-1-yl)acetophenone with a variety of benzyl halides that contain either electron-donating or electron-withdrawing groups. The structures of the new imidazolium salts were conformed using different spectroscopic methods (H-1 NMR, C-13 NMR, F-19 NMR, and FTIR) and elemental analysis techniques. Furthermore, these compounds' the carbonic anhydrase (hCAs) and acetylcholinesterase (AChE) enzyme inhibition activities were investigated. They showed a highly potent inhibition effect toward AChE and hCAs with K-i values in the range of 8.30 & PLUSMN; 1.71 to 120.77 & PLUSMN; 8.61 nM for AChE, 16.97 & PLUSMN; 2.04 to 84.45 & PLUSMN; 13.78 nM for hCA I, and 14.09 & PLUSMN; 2.99 to 69.33 & PLUSMN; 17.35 nM for hCA II, respectively. Most of the synthesized imidazolium salts appeared to be more potent than the standard inhibitor of tacrine (TAC) against AChE and Acetazolamide (AZA) against CA. In the meantime, to prospect for potential synthesized imidazolium salt inhibitor(s) against AChE and hCAs, molecular docking and an ADMET-based approach were exerted.Öğe Benzimidazolium Salts Bearing Nitrile Moieties: Synthesis, Enzyme Inhibition Profiling, and Molecular Docking Analysis for Carbonic Anhydrase and Acetylcholinesterase(Wiley-V C H Verlag Gmbh, 2023) Oner, Erkan; Gok, Yetkin; Demir, Yeliz; Taskin-Tok, Tugba; Aktas, Aydin; Gulcin, Ilhami; Yalin, SerapThis report presents the synthesis and characterization of a range of benzimidazolium salts featuring 3-cyanopropyl groups on the 1st nitrogen atom and varied alkyl groups on the 3rd nitrogen atom within the benzimidazole structure. Benzimidazolium salts were synthesized by N-alkylation of 1-alkyl benzimidazole with 3-cyanopropyl-bromide. The new salts were characterized by 1H and 13C-NMR, FT-IR spectroscopic and elemental analysis techniques. In this study, the enzyme inhibition abilities of seven nitrile substituted benzimidazolium salts were investigated against acetylcholinesterase (AChE) and carbonic anhydrase isoenzymes I and II (hCA I and hCA II). They showed a highly potent inhibition effect on AChE, hCA I and hCA II (Ki values are in the range of 26.71-119.09 nM for AChE, 19.77 to 133.68 nM for hCA I and 13.09 to 266.38 nM for hCA II). Reflecting the binding mode of the synthesized cyanopropyl series, the importance of the 2,3,5,6-tetramethylbenzyl, 3-methylbenzyl and 3-benzyl groups for optimal interactions with target proteins, evaluated by molecular docking studies. At the same time, the docking findings support the inhibition constants (Ki) values of the related compounds in this study. Potential compounds were also evaluated by their pharmacokinetic properties were predicted. imageÖğe Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and ?-glycosidase(Wiley, 2022) Tezcan, Burcu; Gok, Yetkin; Sevincek, Resul; Taslimi, Parham; Taskin-Tok, Tugba; Aktas, Aydin; Guzel, BilgehanHere, we report the synthesis, characterization, and biological activities of a series of benzimidazolium salts bearing the trifluoromethylbenzyl group. All benzimidazolium salts were characterized by using nuclear magnetic resonance (NMR) (H-1 NMR and C-13 NMR), Fourier transform-infrared spectroscopy, and elemental analysis techniques. The crystal structures of some of these compounds were obtained by the single-crystal X-ray diffraction method. Furthermore, the acetylcholinesterase (AChE) and alpha-glycosidase (alpha-Gly) enzyme inhibition activities of these compounds were investigated. The obtained results revealed that 2e, with K-i value of 1.36 +/- 0.34 mu M against AChE and 3d with K-i value of 91.37 +/- 10.38 mu M against alpha-Gly, were the most potent compounds against both assigned enzymes. It should be noted that most of the synthesized compounds were more potent than standard inhibitor tacrine (TAC) against AChE. In silico studies, we focused on compound 2e, 3d, 3e, and 3f as potent inhibitors of AChE and alpha-Gly, the compound 2e showed good binding energy (-10.23 kcal/mol), among the three selected compounds and positive control (-10.18, -10.08, and -7.37 kcal/mol for 3d, 3f, and TAC, respectively). Likewise, as a result of the same compounds against the alpha-Gly enzyme, the compound 3d had the highest binding affinity (-8.39 kcal/mol) between the four selected compounds and the positive control (-8.27, -8.10, -8.06, and -7.53 kcal/mol for 3f, 3e, 2e, and acarbose, respectively). From the absorption, distribution, metabolism, excretion, and toxicity analyses, it can be concluded that the compounds under consideration exhibited more drug-likeness properties in the prediction studies compared to positive controls.Öğe Benzimidazolium Salts Containing Trifluoromethoxybenzyl: Synthesis, Characterization, Crystal Structure, Molecular Docking Studies and Enzymes Inhibitory Properties(Wiley-V C H Verlag Gmbh, 2022) Hamide, Mahmut; Gok, Yetkin; Demir, Yeliz; Sevincek, Resul; Taskin-Tok, Tugba; Tezcan, Burcu; Aktas, AydinThe method for producing 4-trifluoromethoxybenzyl substituted benzimidazolium salts is described in this article. The method is based on the reaction of 4-trifluoromethoxybenzyl substituent alkylating agent with 1-alkylbenzimidazole. This method yielded 1-(4-trifluoromethoxybenzyl)-3-alkylbenzimidazolium bromide salts. These benzimidazolium salts were characterized by using H-1-NMR, C-13-NMR, FT-IR spectroscopy, and elemental analysis techniques. The crystal structure of 1f was enlightened by single crystal X-ray diffraction studies. Also, the enzyme inhibition effects of the synthesised compounds were investigated. They demonstrated highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (K-i values are in the range of 7.24 +/- 0.99 to 39.12 +/- 5.66 nM, 5.57 +/- 0.96 to 43.07 +/- 11.76 nM, and 4.38 +/- 0.43 to 18.68 +/- 3.60 nM for AChE, hCA I, and hCA II, respectively). In molecular docking study, the interactions of active compounds showing activity against AChE and hCAs enzymes were examined. The most active compound 1f has -10.90 kcal/mol binding energy value against AChE enzyme, and the potential structure compound 1e, which has activity against hCA I and hCA II enzymes, was -7.51 and -8.93 kcal/mol, respectively.Öğe Design, synthesis, spectroscopic characterizations, single crystal X-ray analysis, in vitro xanthine oxidase and acetylcholinesterase inhibitory evaluation as well as in silico evaluation of selenium-based N-heterocyclic carbene compounds(Taylor & Francis Inc, 2023) Kaya, Guelsen; Noma, Samir Abbas Ali; Celepci, Duygu Barut; Bayil, Imren; Taskin-Tok, Tugba; Gok, Yetkin; Ates, BurhanHerein, eight new NHC-based selenourea derivatives were synthesized and characterized by using spectroscopic method (H-1, F-19, and C-13 NMR, FT-IR), and elemental analysis techniques. These compounds were synthesized by mixing benzimidazolium salts, potassium carbonate, and selenium powder in ethyl alcohol. Additionally, the molecular and crystal structures of the three compounds (1c, 2b, and 2c) were determined using the single-crystal x-ray diffraction (XRD) method. Diffraction analysis demonstrated the partial carbon-selenium double-bond character of these compounds. All compounds were determined to be highly potent inhibitors for AChE and XO enzymes. The IC(50 )values for the compounds were found in the range of 0.361-0.754 mu M for XO and from 0.995 to 1.746 mu M for AChE. The DNA binding properties of the compounds were investigated. These compounds did not have a remarkable DNA binding property. Also, DPPH radical scavenging activities of the compounds were also investigated. Compounds (1c), (2a), (3a), and (3b) exhibited more pronounced DPPH radical scavenging activity when compared to other compounds. Docking studies were applied by using AutoDock 4 to determine interaction mechanism of the selected compounds (1a), (1b), and (3b). The compound (1b) has good binding affinity (-9.78 kcal/mol) against AChE, and (-6.86 kcal/mol) for XO target. Drug similarity properties of these compounds compared to positive controls were estimated and evaluated by ADMET analysis. Furthermore, molecular dynamics simulations have been applied to understand the accuracy of docking studies. These findings and the defined compounds could be potential candidates for the discovery and progress of effective medicine(s) for AChE and XO in the future.In this study, we synthesized selenourea derivatives from N-heterocyclic carbene (NHC) precursors. All compounds were characterized by using NMR, FTIR spectroscopic method, and elemental analysis technique. In addition, the crystal structure of the three compounds was determined using the single-crystal X-ray diffraction method. New selenoura derivatives were tested for their effect to inhibit the xanthine oxidase and acetylcholinesterase enzymes. The DNA binding properties of the Se-NHC compounds were investigated and the compounds did not have significant DNA binding properties. In addition, DPPH radical scavenging activities of Se-NHC compounds were also investigated. All compounds exhibited DPPH radical scavenging activity. Molecular Docking studies using AutoDock 4 were used to determine the interaction mechanism of selected compounds (1a, 1b, and 3b) Drug similarity properties of these compounds compared to positive controls were estimated and evaluated by ADMET analysis. Furthermore, molecular dynamics simulations have been applied to understand the accuracy of docking studies.Öğe Evaluation of xanthine oxidase inhibitor properties on isoindoline-1,3-dion derivatives and calculation of interaction mechanism(Elsevier, 2020) Gundugdu, Ozlem; Noma, Samir Abbas Ali; Taskin-Tok, Tugba; Ates, Burhan; Kishali, NurhanThe aim of the present study was to synthesis of isoindole-1,3(2H)-dione (Phthalimides) derivatives and to investigation the inhibition of xanthine oxidase (XO). In study, xanthine oxidase inhibitory activities of complexes were observed in the range from 7.15 to 22.56 mu M for isoindole-1,3-dione (2a-c and 3a-c). N-phenyl isoindole-1,3-dione derivatives (2c, 3c) showed better activity (almost two times) than the other two derivatives (N-methyl (2a, 3a), N-ethyl (2b, 3b). It means that phenyl ring (R) remarkably enhances the xanthine oxidase inhibitory effect of complexes. In the meantime, molecular docking studies of these compounds against XO were also investigated by providing the inhibitory efficiency and estimating the interaction mechanisms of isoindol-1,3-dion derivatives with XO. (C) 2019 Elsevier B.V. All rights reserved.Öğe Fluorinated benzimidazolium salts: Synthesis, characterization, molecular docking studies and inhibitory properties against some metabolic enzymes(Elsevier Science Sa, 2023) Zengin, Ramazan; Gok, Yetkin; Demir, Yeliz; Sen, Betul; Taskin-Tok, Tugba; Aktas, Aydin; Demirci, OzlemHere, a number of symmetric and unsymmetric N-heterocyclic carbene (NHC) precursors based on benzimidazol-2-ylidene are synthesized. The N-benzyl substituent in these compounds has an electron-withdrawing group (F) at the para position. The structure of these compounds was characterized using elemental analysis and various spectroscopic methods (FTIR and NMR). The molecular and crystal structures of compound 1f and compound 1h were unambiguously elucidated through single-crystal X-ray diffraction analysis. According to the X-ray studies, compound 1f exhibits the formation of a U-shaped molecule whereas compound 1h has a Z-shape formation. In addition, the enzyme inhibition activities of these compounds were investigated against acetylcholinesterase (AChE) and carbonic anhydrases (hCAs). They showed a highly potent inhibition effect on AChE and hCAs (Ki values are in the range of 14.84 +/- 1.91 to 174.80 +/- 23.60 nM for AChE, 22.41 +/- 1.93 to 188.67 +/- 27.05 nM for hCA I and 35.29 +/- 7.21 to 136.55 +/- 17.61 nM for hCA II). These results may contribute to the design and development of new drug candidates, particularly for treatment of some widespread disorders displayed in the world including Alzheimer's disease and glaucoma.Öğe N-Heterocyclic Compounds, In silico Molecular Docking Studies, and In vitro Enzyme Inhibition Effect against Acetylcholinesterase Inhibitors(Bentham Science Publ Ltd, 2023) Guzel, Abdussamat; Isik, Zeynep; Gok, Yetkin; Taskin-Tok, Tugba; Aktas, AydinBackground: This work contains the synthesis of seven new N-heterocyclic compounds bearing imidazole, benzimidazole, pyridine, and morpholine moieties.Objectives: We aimed to synthesize N-heterocyclic compounds for a more effective drug candidate to increase the amount of acetylcholine in synapses in Alzheimer's disease. All compounds were characterized by H-1 NMR, C-13 NMR, FTIR and elemental analysis. Enzyme inhibition activity of all compounds against acetylcholinesterase was investigated, which is an indirect treatment for Alzheimer's. Molecular docking was applied to estimate the binding energy of these compounds to the acetylcholinesterase.Methods:All compounds were synthesized from reactions of 2 equivalents of N-heterocyclic starting material and 1 equivalent of 4,4'-bis(chloromethyl)-1,1'-biphenyl. The inhibition parameters of IC50 and K-i were calculated by the spectrophotometric method. AutoDock4 was used to define the binding pose of the compounds.Results: K-i values were found in the range of 80.03 +/- 19.64 to 5014.98 +/- 1139.60 nM for AChE as an enzyme inhibition strategy, which is an important parameter for the treatment of neurodegenerative such as Alzheimer's disease. In this study, molecular docking is exerted to predict the binding energy of heterocyclic compounds (especially 2, 3, and 5) against acetylcholinesterase enzyme. Their docking binding energies are in good agreement with experimental findings.Conclusion: These new syntheses are drugs that can be used as AChE inhibitors in Alzheimer's disease.Öğe New palladium complexes with N-heterocyclic carbene and morpholine ligands: Synthesis, characterization, crystal structure, molecular docking, and biological activities(Wiley, 2024) Behcet, Ayten; Taslimi, Parham; Sen, Betul; Taskin-Tok, Tugba; Aktas, Aydin; Gok, Yetkin; Aygun, MuhittinThis work includes the synthesis of a new series of palladium-based complexes containing both morpholine and N-heterocyclic carbene (NHC) ligands. The new complexes were characterized using NMR (1H and 13C), FTIR spectroscopic, and elemental analysis techniques. The crystal structure of complex 1b was obtained by utilizing the single-crystal X-ray diffraction method. X-ray studies show that the coordination environment of palladium atom is completed by the carbene carbon atom of the NHC ligand, the nitrogen atom of the morpholine ring, and a pair of bromide ligand, resulting in the formation of slightly distorted square planar geometry. All complexes were determined for some metabolic enzyme activities. Results indicated that all the synthetic complexes exhibited powerful inhibitory actions against all aims as compared to the control molecules. Ki values of new morpholine-liganded complexes bearing 4-hydroxyphenylethyl group 1a-e for hCA I, hCA II, AChE, BChE, and alpha-glycosidase enzymes were obtained in the ranges 0.93-2.14, 1.01-2.03, 4.58-10.27, 7.02-13.75, and 73.86-102.65 mu M, respectively. Designing of reported complexes is impacted by molecular docking study, and interaction with the current enzymes also proclaimed that compounds 1e (-12.25 kcal/mol for AChE and -11.63 kcal/mol for BChE), 1c (-10.77 kcal/mol and -9.26 kcal/mol for alpha-Gly and hCA II, respectively), and 1a (-8.31 kcal/mol for hCA I) are showing binding affinity and interaction from the synthesized five novel complexes.Öğe New PEPPSI-Pd-NHC complexes bearing 4-hydroxyphenylethyl group: Synthesis, characterization, molecular docking, and bioactivity properties(Wiley-V C H Verlag Gmbh, 2022) Behcet, Ayten; Taslimi, Parham; Gok, Yetkin; Aktas, Aydin; Taskin-Tok, Tugba; Gulcin, IlhamiFive 4-hydroxyphenylethyl substituted pyridine enhanced, precatalyst, preparation, stabilization, and initiation-Pd-N-heterocyclic carbene (PEPPSI-Pd-NHC) complexes are synthesized in a straightforward way. All PEPPSI-Pd-NHC complexes were prepared by mixing 4-hydroxyphenylethyl substituted NHC precursors, palladium chloride, potassium carbonate, and potassium bromide in pyridine. All complexes were screened for human carbonic anhydrase I (hCA I) and hCA II, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glucosidase (alpha-Glu) inhibitory activities. The ChE inhibitory activities of the new PEPPSI-Pd-NHC complexes bearing the 4-hydroxyphenylethyl group (12-e) against alpha-Glu, AChE, and BChE were determined by the Tao and Ellman methods. The results indicated that all the synthetic complexes exhibited potent inhibitory activities against all targets as compared to the standard inhibitors, revealed by IC50 values. The K-i values of the new PEPPSI-Pd-NHC complexes 1a-e for hCA I, hCA II, AChE, BChE, and alpha-Glu were obtained in the ranges of 18.98-32.65, 22.95-38.13, 3.67-11.65, 4.09-9.36, 186.92-287.45 mu M, respectively. Among the synthesized complexes, the most potent complexes were 1c toward hCA I and II with K-i values 18.98 and 22.95 mu M, and 1d toward AChE and BChE with K-i = 3.67 and 4.09 mu M, respectively.Öğe Novel PEPPSI-type N-heterocyclic carbene palladium(II) complexes: Synthesis, characterization, in silico studies and enzyme inhibitory properties against some metabolic enzymes(Elsevier Science Sa, 2023) Yigit, Beyhan; Taslimi, Parham; Celepci, Duygu Barut; Taskin-Tok, Tugba; Yigit, Murat; Aygun, Muhittin; Ozdemir, IsmailIn this study, a series of PEPPSI-type N-heterocyclic carbene palladium(II) complexes 3a-e were synthesized using amine functionalized benzimidazolium salts 2a-e as N-heterocyclic carbene precursors. These complexes were characterized by FT-IR, 1H NMR and 13C NMR spectroscopy, elemental analysis and mass spectrometry. Also, the molecular and crystal structure of 3b has been determined by the single-crystal X-ray diffraction method. According to the structural analysis, the geometry of the palladium center of the complex adopts a slightly distorted square planar environment. The benzimidazolium salts 2a-e and their palladium(II) complexes 3a-e were screened for human carbonic anhydrase I, II (hCAs I and II), and alpha-glycosidase inhibitory activities. Results indicated that all the synthetic compounds exhibited potent inhibitory activities against all targets as compared to the standard inhibitors, revealed by IC50 values. Ki values of 2a-e and 3a-e for hCA I, hCA II, and alpha-glycosidase enzymes were obtained in the ranges 1.17 +/- 0.11-65.50 +/- 8.20 mu M, 1.02 +/- 0.08-57.60 +/- 6.41 mu M, and 118.86 +/- 11.92-509.21 +/- 26.61 nM, respectively. Besides these, molecular docking calculations of potent compounds 2b, 2d, 2e, 3a, 3b, 3c and 3e towards human carbonic anhydrase I (hCA I), human carbonic anhydrase II (hCA II), and alpha-glycosidase (alpha-Gly) were presented using AutoDock 4. Among the compounds discussed, compounds 3c, 3a, 2e and 2b have the best binding affinity for alpha-Gly (-9.87,-9.77,-9.04 and-8.63 kcal/mol); compounds 3e, 3b, 2d and 2e turn out to have the second-best binding affinity (-8.80,-8.74,-8.39 and-7.57 kcal/mol) against hCA II. Lastly, compounds showing the lowest binding affinity for hCA I enzyme are 3e, 3b, 2d and 2e, respectively. These findings show that especially NHC-palladium(II) complexes 3a-e are more active for all three enzyme structures than their N-heterocyclic carbene precursors 2a-e and may be potential candidates for the discovery and development of effective inhibitors for the related enzymes in the future.Öğe Phthalimide-tethered imidazolium salts: Synthesis, characterization, enzyme inhibitory properties, and in silico studies(Wiley-V C H Verlag Gmbh, 2022) Yigit, Murat; Demir, Yeliz; Celepci, Duygu Barut; Taskin-Tok, Tugba; Arinc, Ali; Yigit, Beyhan; Aygun, MuhittinA series of new imidazolium salts were prepared in good yield by the reaction between 1-alkylimidazole and a variety of alkyl halides. The structures of the compounds were identified by FT-IR, H-1 NMR, and C-13 NMR spectroscopy, elemental analysis, and mass spectrometry. The crystal structure of 1b was determined by the single-crystal X-ray diffraction method. The phthalimide-tethered imidazolium salts exhibited inhibition abilities toward acetylcholinesterase (AChE) and human carbonic anhydrases (hCAs) I and II, with K-i values in the range of 24.63 +/- 3.45 to 305.51 +/- 35.98 nM for AChE, 33.56 +/- 3.71 to 218.01 +/- 25.21 nM for hCA I and 17.75 +/- 0.96 to 308.67 +/- 13.73 nM for hCA II. The results showed that the new imidazolium salts can play a key role in the treatment of Alzheimer's disease, epilepsy, glaucoma, and leukemia, which is related to their inhibition abilities of hCA I, hCA II, and AChE. Molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity studies were used to look into how the imidazolium salts interacted with the specific protein targets. To better visualize and understand the binding positions and the influence of the imidazolium salts on hCA I, hCA II, and AChE conformations, each one was subjected to molecular docking simulations.Öğe Synthesis, characterization and inhibitor properties of benzimidazolium salts bearing 4-(methylsulfonyl)benzyl side arms(Elsevier, 2023) Guzel, Abdussamat; Noma, Samir Abbas Ali; Sen, Betul; Kazanci, Ali; Taskin-Tok, Tugba; Kolac, Turgay; Aktas, AydinHerein, a series of N-heterocyclic carbene (NHC) precursors bearing sulfonyl moieties was prepared. 1-(4-(methylsulfonyl)benzyl)-3-alkylbenzimidazolium chloride salts were synthesized with the reaction of 1-alkylbenzimidazoles with 4-(methylsulfonyl)benzyl chloride. These compounds were characterized by using 1 H NMR, 13 C NMR, FT-IR spectroscopy and elemental analysis techniques. Molecular and crystal structures of compounds 2e and 2j were determined by using the single-crystal X-ray diffraction method. Furthermore, enzyme inhibitory properties of benzimidazolium salt were tested against xanthine oxidase (XO) and acetylcholinesterase (AChE), then determined the IC50 value range of XO were determined from 0.218 to 1.927 mu M, while the IC50 for AChE were determined from 1.328 to 5.22. Docking applications were used by using AutoDock4 in order to define the binding pose of the selected compounds, ( 2c, 2d and 2g ) and also to visualize the correlation of the generated optimal complexes. It is found that the compound 2g has good binding affinity (-11.24 kcal/mol) against AChE, on the other side, compound 2c shows the lowest binding energy (-8.32 kcal/mol) for the XO target. These findings and the defined compounds could be as potential agents to develop effective medicine for AChE and XO in the future.(c) 2022 Elsevier B.V. All rights reserved.Öğe Synthesis, characterization, crystal structure, biological activities, and molecular docking study of the (NHC)Pd(II)(Morp) (NHC: N-heterocyclic carbene, Morp: Morpholine) complexes(Pergamon-Elsevier Science Ltd, 2024) Aktas, Aydin; Taslimi, Parham; Bal, Selma; Celepci, Duygu Barut; Gok, Yetkin; Taskin-Tok, Tugba; Aygun, MuhittinIn this paper, a new palladium -based (NHC)Pd(II)(Morp) complexes (NHC: N -heterocyclic carbene, Morp: morpholine) were prepared. The NHC ligand in these complexes bears the 2-chloro-4-fluorobenzyl group. All complexes were fully characterized by 1 H, 13 C NMR, FTIR spectroscopic and elemental analysis methods. The crystal structure of complex 1f has been determined by using single-crystal X-ray diffraction. Furthermore, all complexes were investigated for their ability to inhibit enzymes. All complexes exhibited highly potent inhibition effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes (K i values are in the range of 97.84 +/- 8.97 to 132.28 +/- 11.63 mu M and 18.24 +/- 2.08 to 39.08 +/- 5.28 mu M for AChE and BChE, respectively). Designing of reported complexes is impacted by molecular docking study, because with molecular docking study, it will lead to future researches by illuminating the interaction mechanism of complexes 1a , 1b , 1c and 1f with potential activity against target AChE and BChE enzymes at molecuar level.Öğe Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives(Academic Press Inc Elsevier Science, 2021) Yagiz, Guler; Noma, Samir Abbas Ali; Altundas, Aliye; Al-khafaji, Khattab; Taskin-Tok, Tugba; Ates, BurhanThis study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 mu M. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 mu M, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R-2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores -4.790,-4.755, and -4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.Öğe Thioether-substituted Benzimidazolium Salts: Synthesis, Characterization, Crystal Structure, and Their Inhibitory Properties Against Acetylcholinesterase and Xanthine Oxidase(Elsevier, 2023) Yavuz, Kemal; Noma, Samir Abbas Ali; Sen, Betuel; Taskin-Tok, Tugba; Aktas, Aydin; Ates, Burhan; Osman, BilgenThe sulfurous compounds are known as organosulfur, which has been associated with numerous biological activities in both natural products and synthetic organic compounds. In this work, we present the synthesis of a series of 4-(methylthio)benzyl substituted benzimidazolium salts. All compounds were characterized using NMR (1H and 13C) and FTIR spectroscopic methods as well as an elemental analysis technique. The molecular and crystal structures of the compound 1a were determined by X-ray crystallography revealing that the compound crystallized in the trigonal space group R-3. Enzyme inhibition studies demonstrated that a new series of sulfurous compounds precursors were highly potent inhibitors for xanthine oxidase (XO) and acetylcholinesterase (AChE) enzyme. The IC50 values were found in the range of 0.548 +/- 0.033 to 0.725 +/- 0.043 mu M for XO promising strategy for the treatment from gout disease, while IC50 values were found in the range 0.813 +/- 0.076 to 1.149 +/- 0.072 mu M toward AChE as the key enzyme promising strategy for the treatment of neurological disorders such as Alzheimer's disease (AD). Furthermore, pharmacodynamics studies prove the binding interaction patterns, structural orientations and drug potential of sulfide derivatives in the binding sites of xanthine oxidase (XO) and acetylcholinesterase (AChE) enzymes. Potential inhibitors (compounds 1d-f) were compared with standard compounds allopurinol (for XO) and donepezil (for AChE). Compared to the positive compound of target XO, the 4-vinylbenzyl group of potential compound 1f and the 4-methylbenzyl group of compound le more effectively formed electrostatic and hydrophobic interactions with the target's interaction site. While donepezil as standard compound interacts only at the peripheral anionic site of AChE, the related compounds interact with both regions (PAS and CAS sites) of the same target. These compounds were placed at the active sites of the respective targets by molecular docking method using AutoDock software. Binding energy, binding modes and interaction types were used to evaluate the series of 4-(methylthio)benzyl substituted benzimidazolium salts's ability to bind to each target. Binding energy lower than zero remarks spontaneous binding, and equal and/or lower than -5 kcal/mol remarks good binding. Besides XO, the related compounds show higher activity against the AChE enzyme. They can also be analyzed as strong candidate compounds in biological studies of related enzymes.
