108 results on '"Ulviye Acar Çevik"'
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2. Synthesis, characterization, antimicrobial, antioxidant, and anti-cancer activity of new hybrid structures based on benzimidazole and thiadiazole
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Hayrani Eren Bostancı, Ulviye Acar Çevik, Ayşen Işık, Zahra Maryam, Ufuk İnce, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Benzimidazole ,Thiadiazole ,Antimicrobial ,Anti-cancer ,Antioxidant ,Pharmacy and materia medica ,RS1-441 - Abstract
Abstract Hybrid structures containing multiple pharmacophore units with known activity have attracted attention due to their promising outcomes. In this study, several new hybrid structures containing benzimidazole and thiadiazole units were synthesized. The newly synthesized compounds were structurally analyzed using 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antimicrobial, in vitro anti-cancer, and antioxidant activities of all compounds were investigated. In vitro antimicrobial activities of the compounds were determined against Gram-positive (S. aureus ATCC 29213, E. faecalis ATCC 29212), Gram-negative (E. coli ATCC 25922, P. aeruginosa ATCC 27853) bacteria and fungi (C. albicans ATCC 10231) by using broth microdilution method. The compound 5g bearing 4-methoxyphenyl derivative showed the best activity with 32 μg/mL against S. aureus ATCC 29213 and P. aeruginosa ATCC 27853. The MTT test was used to determine the cytotoxicity of the produced compounds on the MCF-7 (human breast cancer) and L-929 (fibroblast) cell lines. FRAP method was used to determine the antioxidant properties of synthesized compounds. The Ferric Reducing Antioxidant Power of the compounds 5a, 5b, and 5c showed more antioxidant properties than vitamin E. The compound 5g stands out in the series in that it is not toxic on the healthy cell line and has promising antimicrobial activity.
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- 2025
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3. Synthesis, DFT Calculations, In Silico Studies, and Antimicrobial Evaluation of Benzimidazole-Thiadiazole Derivatives
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Ayşen Işık, Ulviye Acar Çevik, Arzu Karayel, Iqrar Ahmad, Harun Patel, İsmail Çelik, Ülküye Dudu Gül, Gizem Bayazıt, Hayrani Eren Bostancı, Ahmet Koçak, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Chemistry ,QD1-999 - Published
- 2024
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4. New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies
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Ulviye Acar Çevik, Betül Kaya, Ismail Celik, Mithun Rudrapal, Gourav Rakshit, Arzu Karayel, Serkan Levent, Derya Osmaniye, Begüm Nurpelin Sağlık Özkan, Merve Baysal, Özlem Atlı Ekliog̈lu, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Chemistry ,QD1-999 - Published
- 2024
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5. Design, Synthesis, and Biological Effect Studies of Novel Benzofuran–Thiazolylhydrazone Derivatives as Monoamine Oxidase Inhibitors
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Derya Osmani̇ye, Begüm Nurpelin Sağlik, Serkan Levent, Ulviye ACAR Çevi̇k, Sinem Ilgin, Leyla Yurttaş, Yusuf Özkay, Ahmet Cagri Karaburun, Zafer Asım Kaplancikli, and Nalan Gundogdu-Karaburun
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Chemistry ,QD1-999 - Published
- 2024
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6. Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole–Thiadiazole Hybrids
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Ismail Celik, Ulviye Acar Çevik, Arzu Karayel, Ayşen Işık, Uğur Kayış, Ülküye Dudu Gül, Hayrani Eren Bostancı, Süheyl Furkan Konca, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Chemistry ,QD1-999 - Published
- 2022
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7. Synthesis, in vitro enzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors
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Begüm Nurpelin Sağlık, Derya Osmaniye, Ulviye Acar Çevik, Serkan Levent, Betül Kaya Çavuşoğlu, Özlem Atlı Eklioğlu, Yusuf Özkay, Ali Savaş Koparal, and Zafer Asım Kaplancıklı
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benzylamine ,enzyme inhibition ,heterocyclic ring ,mao enzymes ,molecular docking ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Many studies have been conducted on the selective inhibition of human monoamine oxidase B (hMAO-B) enzyme using benzylamine-sulphonamide derivatives. Using various chemical modifications on BB-4h, which was reported previously by our team and showed a significant level of MAO-B inhibition, novel benzylamine-sulphonamide derivatives were designed, synthesised, and their MAO inhibition potentials were evaluated. Among the tested derivatives, compounds 4i and 4t achieved IC50 values of 0.041 ± 0.001 µM and 0.065 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition by compounds 4i and 4t was studied using Lineweaver–Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds 4i and 4t were found to be non-toxic. Molecular docking studies were also carried out for compound 4i, which was found as the most potent agent, within hMAO-B catalytic site.
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- 2020
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8. Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison
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Ulviye Acar Çevik, Begüm Nurpelin Sağlık, Derya Osmaniye, Serkan Levent, Betül Kaya Çavuşoğlu, Abdullah Burak Karaduman, Özlem Atlı Eklioğlu, Yusuf Özkay, and Zafer Asım Kaplancıklı
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benzimidazole ,1,3,4-oxadiazole ,anticancer ,dna topo i ,hoechst 33342 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
In this study, some benzimidazole-oxadiazole derivatives were synthesised and tested for their in vitro anticancer activities on five cancer cell lines, including HeLa, MCF7, A549, HepG2 and C6. Their structures were elucidated by IR, 1H-NMR, 13C-NMR, 2 D-NMR and HRMS spectroscopic methods. Among all screened compounds; 5a, 5b, 5d, 5e, 5k, 5l, 5n and 5o exhibited potent selective cytotoxic activities against various tested cancer cell lines. Especially, compounds 5l and 5n exhibited the most antiproliferative activity than Hoechst 33342 and doxorubicin against HeLa cell line, with IC50 of 0.224 ± 0.011 µM and 0.205 ± 0.010 µM, respectively. Furthermore, these potent lead cytotoxic agents were evaluated in terms of their inhibition potency against Topoisomerase I and it was determined that selected compounds inhibited the Topoisomerase I. Docking studies were performed and probable interactions in the DNA-Topo I enzyme complex was determined.
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- 2020
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9. Design, synthesis, and evaluation of novel 2-phenylpropionic acid derivatives as dual COX inhibitory-antibacterial agents
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Hülya Karaca Gençer, Ulviye Acar Çevik, Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Serkan Levent, Özlem Atlı, Sinem Ilgın, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Phenylpropionic acid ,COX inhibition ,antibacterial ,dual effect ,docking ,Therapeutics. Pharmacology ,RM1-950 - Published
- 2017
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10. Design, Synthesis, and Structure–Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer’s Disease
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Begüm Nurpelin Sağlık, Derya Osmaniye, Ulviye Acar Çevik, Serkan Levent, Betül Kaya Çavuşoğlu, Yusuf Özkay, and Zafer Asım Kaplancıklı
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ADME parameters ,Alzheimer’s disease ,anticholinesterase enzyme activity ,molecular docking ,thiazole ,Organic chemistry ,QD241-441 - Abstract
Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 µM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 µM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.
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- 2020
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11. Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors
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Begüm Nurpelin Sağlık, Osman Cebeci, Ulviye Acar Çevik, Derya Osmaniye, Serkan Levent, Betül Kaya Çavuşoğlu, Sinem Ilgın, Yusuf Özkay, and Zafer Asım Kaplancıklı
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ADME properties ,in vitro enzyme inhibition ,molecular docking ,monoamine oxidases ,thiazolylhydrazine ,piperazine ,Organic chemistry ,QD241-441 - Abstract
Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as 1H-NMR, 13C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds 3c, 3d and 3e displayed significant MAO-A inhibition potencies. Among them, compound 3e was found to be the most effective derivative with an IC50 value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC50 = 6.061 ± 0.262 µM) and clorgiline (IC50 = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound 3e and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property.
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- 2020
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12. Design, Synthesis, and Biological Activity Evaluation of New Donepezil-Like Compounds Bearing Thiazole Ring for the Treatment of Alzheimer’s Disease
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Begüm Nurpelin Sağlık, Serkan Levent, Derya Osmaniye, Ulviye Acar Çevik, Betül Kaya Çavuşoğlu, Yusuf Özkay, Ali Savaş Koparal, and Zafer Asım Kaplancıklı
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Alzheimer’s disease ,anticholinesterase enzyme activity ,beta amyloid plaque inhibition ,donepezil ,molecular docking ,thiazolylhydrazone ,Crystallography ,QD901-999 - Abstract
Alzheimer’s disease (AD) is a progressive and neurodegenerative disease that is primarily seen in the elderly population and is clinically characterized by memory and cognitive impairment. The importance of the disease has increased as a result of etiology of the disease having not yet been determined, an increase in patient population over the years, absence of radical treatment, high cost of treatment and care, and significant reduction in the quality of life of the patients, which have led researchers to direct more attention to this field. In a recent study, new indan-thiazolylhydrazone derivatives were designed and synthesized based on the chemical structure of the donepezil molecule, which is the most preferred and has the most appropriate response in the treatment of AD. The structures of the compounds were determined by 1H-NMR and 13C-NMR, and mass spectroscopic methods. Inhibition studies on the cholinesterase (ChE) enzymes and beta amyloid plaque inhibition test of the compounds were performed. Among the synthesized derivatives, compounds 2a, 2e, 2i, and 2l showed potent inhibitory activity on the AChE enzyme. Compound 2e was found to be the most active agent, with an IC50 value of 0.026 µM. The mechanism of AChE inhibition by compound 2e was studied using the Lineweaver-Burk plot, and the nature of inhibition was also determined to be mix-typed. Molecular docking studies were also carried out for compound 2e, which was found as the most potent agent within the AChE enzyme active site. Moreover, compounds 2a, 2e, 2i, and 2l displayed the ability to prevent beta amyloid plaque aggregation at varying rates. In addition, ADME (Absorption, Distribution, Metabolism, Elimination) parameters were evaluated for all synthesized compounds using the QikProp 4.8 software (Schrödinger Inc., NY, USA).
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- 2020
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13. Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
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Ulviye Acar Çevik, Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Derya Osmaniye, Serkan Levent, Sinem Ilgın, Yusuf Özkay, and Zafer Asım Kaplancıklı
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aromatase ,MCF-7 ,NIH3T3 ,benzimidazole ,triazolothiadiazine ,docking ,Organic chemistry ,QD241-441 - Abstract
In the last step of estrogen biosynthesis, aromatase enzyme catalyzes the conversion of androgens to estrogens. Aromatase inhibition is an important way to control estrogen-related diseases and estrogen levels. In this study, sixteen of benzimidazole-triazolothiadiazine derivatives have been synthesized and studied as potent aromatase inhibitors. First, these compounds were tested for their anti-cancer properties against human breast cancer cell line (MCF-7). The most active compounds 5c, 5e, 5k, and 5m on MCF-7 cell line were subject to further in vitro aromatase enzyme inhibition assays to determine the possible mechanisms of action underlying their activity. Compound 5e showed slight less potent aromatase inhibitory activity than that of letrozole with IC50 = 0.032 ± 0.042 µM, compared to IC50 = 0.024 ± 0.001 µM for letrozole. Furthermore, compound 5e and reference drug letrozole were docked into human placental aromatase enzyme to predict their possible binding modes with the enzyme. Finally, ADME parameters (absorption, distribution, metabolism, and excretion) of synthesized compounds (5a–5p) were calculated by QikProp 4.8 software.
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- 2020
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14. Synthesis and AChE Inhibitory Activity of Novel Thiazolylhydrazone Derivatives
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Derya Osmaniye, Begüm Nurpelin Sağlık, Ulviye Acar Çevik, Serkan Levent, Betül Kaya Çavuşoğlu, Yusuf Özkay, Zafer Asım Kaplancıklı, and Gülhan Turan
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thiazolylhydrazone ,acetylcholinesterase ,butyrylcholinesterase ,enzyme inhibition ,docking ,Organic chemistry ,QD241-441 - Abstract
Alzheimer’s disease (AD) is the most common of the degenerative brain diseases and is described together with the impairment of cognitive function. Patients with AD lose the capability to code new memories, and life conditions are extremely difficult. The development of new drugs in this area continues at a great pace. A novel series of thiazole-piperazine hybrids, aimed against Alzheimer’s disease (AD), have been synthesized. The structure identification of synthesized compounds was elucidated by 1HNMR, 13C-NMR, and LCMSMS spectroscopic methods. The inhibitory potential of the synthesized compounds on cholinesterase enzymes was investigated. The compounds 3a, 3c and 3i showed significant inhibitory activity on the acetylcholinesterase (AChE) enzyme. On the other hand, none of the compounds showed significant inhibitory activity on the butyrylcholinesterase (BChE) enzyme. In addition to enzyme inhibition studies, enzyme kinetic studies were performed to observe the effects of the most active inhibitor compounds on the substrate−enzyme relationship. In addition to in vitro tests, docking studies also indicated that compound 3c potentially acts as a dual binding site AChE inhibitor.
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- 2019
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15. Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors
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Nafiz Öncü Can, Ulviye Acar Çevik, Begüm Nurpelin Sağlık, Serkan Levent, Büşra Korkut, Yusuf Özkay, Zafer Asım Kaplancıklı, and Ali Savaş Koparal
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Chemistry ,QD1-999 - Abstract
Due to anticandidal importance of azole compounds, a new series of benzimidazole-triazole derivatives (5a–5s) were designed and synthesized as ergosterol inhibitors. The chemical structures of the target compounds were characterized by spectroscopic methods. The final compounds were screened for antifungal activity against Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019), and Candida albicans (ATCC 24433). Compounds 5i and 5s exhibited significant inhibitory activity against Candida strains with MIC50 values ranging from 0.78 to 1.56 μg/mL. Cytotoxicity results revealed that IC50 values of compounds 5i and 5s against NIH/3T3 are significantly higher than their MIC50 values. Effect of the compounds 5i and 5s against ergosterol biosynthesis was determined by LC-MS-MS analysis. Both compounds caused a significant decrease in the ergosterol level. The molecular docking studies were performed to investigate the interaction modes between the compounds and active site of lanosterol 14-α-demethylase (CYP51), which is as a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for final compounds.
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- 2017
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16. Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds
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Ahmet Çağrı Karaburun, Betül Kaya Çavuşoğlu, Ulviye Acar Çevik, Derya Osmaniye, Begüm Nurpelin Sağlık, Serkan Levent, Yusuf Özkay, Özlem Atlı, Ali Savaş Koparal, and Zafer Asım Kaplancıklı
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benzimidazole ,1,3,4-oxadiazole ,antifungal activity ,ergosterol biosynthesis ,cytotoxicity ,molecular docking ,Organic chemistry ,QD241-441 - Abstract
Discovery of novel anticandidal agents with clarified mechanisms of action, could be a rationalist approach against diverse pathogenic fungal strains due to the rise of resistance to existing drugs. In support to this hypothesis, in this paper, a series of benzimidazole-oxadiazole compounds were synthesized and subjected to antifungal activity evaluation. In vitro activity assays indicated that some of the compounds exhibited moderate to potent antifungal activities against tested Candida species when compared positive control amphotericin B and ketoconazole. The most active compounds 4h and 4p were evaluated in terms of inhibitory activity upon ergosterol biosynthesis by an LC-MS-MS method and it was determined that they inhibited ergosterol synthesis concentration dependently. Docking studies examining interactions between most active compounds and lanosterol 14-α-demethylase also supported the in vitro results.
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- 2019
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17. Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Potent Antifungal Agents
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Ahmet Çağrı Karaburun, Ulviye Acar Çevik, Derya Osmaniye, Begüm Nurpelin Sağlık, Betül Kaya Çavuşoğlu, Serkan Levent, Yusuf Özkay, Ali Savaş Koparal, Mustafa Behçet, and Zafer Asım Kaplancıklı
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1,3,4-thiadiazole ,thione-thiol tautomerism ,docking ,antifungal ,14-α-sterol demethylase ,ADME ,Organic chemistry ,QD241-441 - Abstract
With the goal of obtaining a novel bioactive compound with significant antifungal activity, a series of 1,3,4-thiadiazole derivatives (3a⁻3l) were synthesized and characterized. Due to thione-thiol tautomerism in the intermediate compound 2, type of substitution reaction in the final step was determined by two-dimensional (2D) NMR. In vitro antifungal activity of the synthesized compounds was evaluated against eight Candida species. The active compounds 3k and 3l displayed very notable antifungal effects. The probable mechanisms of action of active compounds were investigated using an ergosterol quantification assay. Docking studies on 14-α-sterol demethylase enzyme were also performed to investigate the inhibition potency of compounds on ergosterol biosynthesis. Theoretical absorption, distribution, metabolism, and excretion (ADME) predictions were calculated to seek their drug likeness of final compounds. The results of the antifungal activity test, ergosterol biosynthesis assay, docking study, and ADME predictions indicated that the synthesized compounds are potential antifungal agents, which inhibit ergosterol biosynthesis probably interacting with the fungal 14-α-sterol demethylase.
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- 2018
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18. Synthesis and Biological Evaluation of New Thiosemicarbazone Derivative Schiff Bases as Monoamine Oxidase Inhibitory Agents
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Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Derya Osmaniye, Serkan Levent, Ulviye Acar Çevik, Abdullah Burak Karaduman, Yusuf Özkay, and Zafer Asım Kaplancıklı
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thiosemicarbazone ,MAO-A ,MAO-B ,docking ,MTT ,enzyme kinetic study ,ADME ,Organic chemistry ,QD241-441 - Abstract
Twenty-six novel thiosemicarbazone derivative B1–B26 were synthesized via condensation reactions between the corresponding thiosemicarbazides and aldehydes. The chemical characterization of the compounds was carried out by infrared (IR), mass (MS), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR) spectroscopic analyses. The compounds were investigated for their monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitory activity and most of them were more potent against MAO-A enzyme when compared with MAO-B enzyme. N-Cyclohexyl-2-[4-[(4-chlorophenyl)thio]benzylidene]hydrazine-1-carbothioamide (B24) was the most active compound against MAO-A. The enzyme kinetics study revealed that compound B24 has a reversible and competitive mode of binding. Interaction modes between compound B24 and MAO-A were clarified by docking studies. In addition, the favourable absorption, distribution, metabolism, and excretion (ADME) properties and non-toxic nature of compound B24 make this compound a promising MAO-A inhibitor.
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- 2017
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19. Design and Synthesis of New Benzothiazole Compounds as Selective hMAO-B Inhibitors
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Sinem Ilgın, Derya Osmaniye, Serkan Levent, Begüm Nurpelin Sağlık, Ulviye Acar Çevik, Betül Kaya Çavuşoğlu, Yusuf Özkay, and Zafer Asım Kaplancıklı
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benzothiazole ,hydrazone ,MAO enzyme inhibition ,docking study ,cytotoxicity ,Organic chemistry ,QD241-441 - Abstract
In the current work a new class of novel benzothiazole-hydrazone derivatives was designed and synthesized as hMAO-B inhibitors. Structures of the obtained compounds (3a–3j) were characterized by IR, 1H-NMR, 13C-NMR, and HRMS spectroscopic methods. The inhibitory activity of compounds (3a–3j) against hMAO-A and hMAO-B enzymes was evaluated by using an in vitro fluorometric method. According to activity results, some of the synthesized compounds displayed selective and significant hMAO-B enzyme inhibitor activity. Compound 3e was the most active derivative in the series with an IC50 value of 0.060 µM. Furthermore, cytotoxicity of compound 3e was investigated and found to be non-cytotoxic. Absorption, distribution, metabolism, and excretion (ADME) and blood-brain barrier (BBB) permeability predictions were performed for all compounds. It was determined that these compounds may have a good pharmacokinetic profiles. Bınding modes between the most active compound 3e and the hMAO-B enzyme were analyzed by docking studies. It was observed that there is a strong interaction between compound 3e and enzyme active site.
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- 2017
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20. Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity
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Serkan Levent, Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Derya Osmaniye, Ulviye Acar Çevik, Özlem Atlı, Yusuf Özkay, and Zafer Asım Kaplancıklı
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1,3,4-oxadiazole ,1,3,4-thiadiazole ,antifungal activity ,ergosterol ,cytotoxicity ,docking ,Organic chemistry ,QD241-441 - Abstract
In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds (6a–6s) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Compounds were tested against four Candida species by broth microdilution assay. Compounds 6e, 6k and 6r, bearing a nitro group, showed significant antifungal activity against all fungi with minimum inhibitory concentration (MIC) in the range of 0.78–3.12 µg/mL. These compounds were also screened for their in vitro cytotoxic effects by MTT assay and detected as nontoxic at their active concentrations against Candida strains. To examine the effects of these compounds on ergosterol biosynthesis, the LC-MS-MS method, which is based on quantification of ergosterol level in C. krusei, was carried out. Finally, the most active molecule (6e) was docked in the active site of the lanosterol 14α-demethylase enzyme, and it was determined that there is a strong interaction between the compound and enzyme.
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- 2017
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21. Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives
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Zafer Asım Kaplancıklı, Serkan Levent, Derya Osmaniye, Begüm Nurpelin Sağlık, Ulviye Acar Çevik, Betül Kaya Çavuşoğlu, Yusuf Özkay, and Sinem Ilgın
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benzimidazole ,thiazole ,anticandidal ,docking studies ,CYP51 ,cytotoxicity ,ergosterol ,Organic chemistry ,QD241-441 - Abstract
Azole-based antifungal agents constitute one of the important classes of antifungal drugs. Hence, in the present work, 12 new benzimidazole-thiazole derivatives 3a–3l were synthesized to evaluate their anticandidal activity against C. albicans, C. glabrata, C. krusei, and C. parapsilopsis. The structures of the newly synthesized compounds 3a–3l were confirmed by IR, 1H-NMR, 13C-NMR, and ESI-MS spectroscopic methods. ADME parameters of synthesized compounds 3a–3l were predicted by an in-slico study and it was determined that all synthesized compounds may have a good pharmacokinetic profile. In the anticandidal activity studies, compounds 3c and 3d were found to be the most active compounds against all Candida species. In addition, cytoxicity studies showed that these compounds are nontoxic with a IC50 value higher than 500 µg/mL. The effect of compounds 3c and 3d on the ergosterol level of C. albicans was determined by an LC-MS-MS method. It was observed that both compounds cause a decrease in the ergosterol level. A molecular docking study including binding modes of 3c to lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol biosynthesis, was performed to elucidate the mechanism of the antifungal action. The docking studies revealed that there is a strong interaction between CYP51 and the most active compound 3c.
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- 2017
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22. Synthesis, Anticandidal Activity and Molecular Docking Study of Some New Imidazole Derivatives
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Begüm Nurpelin Sağlık, Ayşen Işık, Ulviye Acar Çevik, Yusuf Özkay, and Serkan Levent
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n/a ,General Works - Abstract
The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents [1–3]. [...]
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- 2017
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23. Design, Synthesis Molecular Docking Study and Antifungal Activity Evaluation of New Benzimidazole-Triazole Derivatives
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Büşra Korkut, Ulviye Acar Çevik, Yusuf Özkay, and Özlem Atlı
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n/a ,General Works - Abstract
Lanosterol 14α-demethylase (CYP51) is an essential enzyme in the fungal life cycle and also an important target for antifungal drug development. Selective inhibition of the enzyme would cause depletion of ergosterol and accumulation of lanosterol and result in the growth inhibition of the fungal cell [1]. [...]
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- 2017
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24. Synthesis and Antimicrobial Activity of Newly Synthesized 2-((5-(4-(5(6)fluoro-1H-benzo[d]imidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio)-Derivatives
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Abdullah Burak Karaduman, Ulviye Acar Çevik, Derya Osmaniye, Yusuf Özkay, and Sinem Ilgın
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n/a ,General Works - Abstract
Benzimidazole derivatives have a great deal of interest in terms of antimicrobial therapy. [...]
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- 2017
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25. Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives
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Ümide Demir Özkay, Ceren Kaya, Ulviye Acar Çevik, and Özgür Devrim Can
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activity cage ,antidepressant ,benzothiazole ,modified forced swimming test ,tail suspension test ,Organic chemistry ,QD241-441 - Abstract
Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.
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- 2017
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26. Pharmacological and Toxicological Screening of Novel Benzimidazole-Morpholine Derivatives as Dual-Acting Inhibitors
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Nafiz Öncü Can, Ulviye Acar Çevik, Begüm Nurpelin Sağlık, Yusuf Özkay, Özlem Atlı, Merve Baysal, Ümide Demir Özkay, and Özgür Devrim Can
- Subjects
benzimidazoles ,morpholines ,AChE ,MAO ,COX ,Organic chemistry ,QD241-441 - Abstract
The aim of this study was to investigate acetylcholinesterase (AChE), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibitory, and antimicrobial activities of a new series of 2-(4-substituted phenyl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole derivatives, for their possible use as multi-action therapeutic agents. Target compounds (n = 15) were synthesized under microwave irradiation conditions in two steps, and their structures were elucidated by FT-IR, 1H-NMR, 13C-NMR and high resolution mass spectroscopic analyses. Pharmacological screening studies revealed that two of the compounds (2b and 2j) have inhibitory potential on both COX-1 and COX-2 enzymes. In addition, cytotoxic and genotoxic properties of the compounds 2b, 2j and 2m were investigated via the well-known MTT and Ames tests, which revealed that the mentioned compounds are non-cytotoxic and non-genotoxic. As a concise conclusion, two novel compounds were characterized as potential candidates for treatment of frequently encountered inflammatory diseases.
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- 2017
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27. New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation
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Hülya Karaca Gençer, Ulviye Acar Çevik, Serkan Levent, Begüm Nurpelin Sağlık, Büşra Korkut, Yusuf Özkay, Sinem Ilgın, and Yusuf Öztürk
- Subjects
1,2,4-triazole ,antifungal activity ,ergosterol ,cytotoxicity ,NIH/3T3 ,Organic chemistry ,QD241-441 - Abstract
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, 1H-NMR, 13C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m, 5o, 5r, 5t, 5y, 5ab, and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m, 5o, 5r, 5w, 5y, 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol.
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- 2017
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28. Benzimidazol-Tiyadiazol Türevlerinin Sentezi, Karakterizasyonu, Antioksidan ve Antikanser Çalışmaları
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Hayrani Eren BOSTANCI and Ulviye ACAR ÇEVİK
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General Medicine - Abstract
Çalışmamızda yeni antikanser ilaçlar geliştirmek üzere bazı benzimidazol-tiyadiazol türevi bileşikler tasarlanmış ve yapıları 1H-NMR,13C-NMR ve elemental analiz spektral verileriyle kanıtlanmıştır. Bileşiklerin sitotoksik aktiviteleri HT29 hücre hattı üzerinde MTT yöntemi kullanılarak referans bileşik florourasilile kıyaslanarak değerlendirilmiştir. Ayrıca, bileşiklerin seçiciliklerini tespit etmek amacıyla L929 (sağlıklı fare fibroblast hücresi) hücre hattına karşı sitotoksik etkisi değerlendirilmiştir. Bileşiklerin IC50 değerleri incelendiğinde, 5-(2-(2,6-dimetoksifenil)-1H-benz[d]imidazol-5(6)-il)-N-siklohekzil-1,3,4-tiyadiazol-2-amin yapısına sahip BT-2 bileşiği 34,13±2,48 µM IC50 değeri ile referans ilaç fluorourasil (12,84 ± 3,66 µM) ile kıyaslanabilir etki göstermiştir. BT-2 bileşiğinin L929 sağlıklı hücre hattı üzerindeki sitotoksik etkisinin referans ilaçtan daha düşük olduğu tespit edilmiştir. Bu sonuçlar, BT-2 bileşiğinin antikanser etkisinin geliştirilebilmesi konusunda umut vericidir. Ayrıca, TAS ve TOS ile bileşiklerin antioksidan özellikleri değerlendirilmiştir. BT-2 bileşiğinin TOS değerinin kontrol ilaçla karşılaştırılabilir düzeyde olduğu görülmüştür.
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- 2022
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29. Design and Synthesis of Imidazole Derivatives as Anticancer Agents and Potential Aromatase Inhibitors
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Hayrani Eren BOSTANCI and Ulviye ACAR ÇEVİK
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Farmakoloji ve Eczacılık ,General Medicine ,İmidazole ,MTT ,Anticancer ,Aromatase ,Pharmacology and Pharmacy - Abstract
In this study, imidazole derivative compounds were synthesized using the Debus-Radziszewski method. The chemical structures of the compounds were characterized by spectroscopic methods. The effects of target compounds on MCF7 (CRL-3435) were examined and their IC50 values and percent viability were calculated. In addition, the cytotoxic effects on the L929 (CCL-1) normal cell line were evaluated in order to determine the selectivities of the compounds. Then, the inhibition values of aromatase enzyme of the compounds were calculated and compared to the reference compound. When the results were examined, it was observed that Compound la caused the death of breast cancer cells, although not as much as cisplatin, but did not harm healthy cells. In this respect, it was determined that compound Ia has a promising anticancer effect as an aromatase inhibitor.
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- 2022
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30. Analgesic and Anti-Inflammatory Potential of Indole Derivatives
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Mithun Rudrapal, Ismail Celik, Sampath Chinnam, Ulviye Acar Çevik, Trina Ekawati Tallei, Aatika Nizam, Francis Joy, Magda H. Abdellattif, and Sanjay G. Walode
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Polymers and Plastics ,Organic Chemistry ,Materials Chemistry - Published
- 2022
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31. Synthesis of Some 2-Substituted-5-(Benzothiazol-2-yl)-1H-Benzimidazole Derivatives and Investigation of Their Antiproliferative Effects
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Bilge Uzun Polat, Ulviye Acar Çevik, Miriş Dikmen, and Yusuf Özkay
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Pharmacology ,Drug Discovery - Published
- 2022
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32. Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4‐Thiadiazole Derivatives as Potent Antimicrobial Agents
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Ulviye Acar Çevik, Ismail Celik, Ufuk İnce, Zahra Maryam, Iqrar Ahmad, Harun Patel, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Molecular Medicine ,Bioengineering ,General Chemistry ,General Medicine ,Molecular Biology ,Biochemistry - Published
- 2023
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33. New benzimidazole‐oxadiazole derivatives: Synthesis, α‐glucosidase, α‐amylase activity, and molecular modeling studies as potential antidiabetic agents
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Ulviye Acar Çevik, Ismail Celik, Leyla Paşayeva, Hanifa Fatullayev, Hayrani E. Bostancı, Yusuf Özkay, and Zafer A. Kaplancıklı
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Drug Discovery ,Pharmaceutical Science - Published
- 2023
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34. Benzimidazole-hydrazone derivatives: Synthesis, in vitro anticancer, antimicrobial, antioxidant activities, in silico DFT and ADMET studies
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Ayşen IŞIK, Ulviye Acar Çevik, Ismail Çelik, Hayrani Eren Bostancı, Arzu Karayel, Gülsüm Gündoğdu, Ufuk Ince, Ahmet Koçak, Yusuf Özkay, Zafer Asım Kaplancıklı, and Eczacılık Fakültesi
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Inorganic Chemistry ,Organic Chemistry ,Benzimidazole Anticancer Antimicrobial Antioxidant DFT ADMET PXRD ,Spectroscopy ,Analytical Chemistry - Abstract
Based on the biologically active heterocycle compounds, a series of new benzimidazole-hydrazone deriva- tives ( 3a-3j ) were synthesized, starting from 4-(6-chloro-1 H -benzimidazol-2-yl) benzohydrazide. The syn- thesized compounds were characterized by 1 H NMR, 13 C NMR, and HRMS spectroscopic methods. The synthesized compounds were preliminarily evaluated for their in vitro antimicrobial, anticancer and an- tioxidant activity. The antimicrobial activity was checked against S. aureus ATCC 29213, E. coli ATCC 25922, and C. albicans ATCC 10231 by micro-dilution method. The findings exhibited that the compounds pos- sessed moderate antimicrobial potential. The compounds were also checked for their in vitro anticancer activities against HT-29 (colorectal cancer cell line) using the MTT assay. It was observed that all the compounds 3a-3j showed weak antiproliferative activity against HT-29 cells. The compounds were also analyzed for their antioxidant capacity by Tas & Tos activity. The compound 3d showed a high anti- oxidative effect with 30.81 μmol H O 2 2 Equiv./L value. The lowest energy state of compound 3d was real- ized in DMSO medium by using the B3LYP method at 6–311G (d,p) level, the optimized geometry of it is about 0.50 and 17 kcal/ mol more stable than in other solvents and the gas phase, respectively. The lower E = 3.563 eV indicates the higher reactivity of compound 3d , this is compatible with biological experi- mental data and shows high antioxidant property of the compound. In silico ADMET studies of compound 3d were performed. Indexing of the X-ray powder diffraction pattern was performed for compound 3a .
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- 2022
35. Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors
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Ayşen Işık, Ulviye Acar Çevik, Ismail Celik, Tuğba Erçetin, Ahmet Koçak, Yusuf Özkay, and Zafer Asım Kaplancıklı
- Subjects
General Biochemistry, Genetics and Molecular Biology - Abstract
In this study, two novel series of thiazolylhydrazone derivatives containing 4-ethylpiperazine (3a–3f) and 4-methoxyphenylpiperazine (3g–3l) side chains were synthesized and their structures were characterized by spectral (1H NMR, 13C NMR, and MS spectra) analyses. In vitro inhibitory activities of synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined by Ellman method. According to the results, all compounds showed a weak inhibitory effect on AChE, while promising results were obtained on BChE. Among the synthesized compounds, the activities of the derivatives carrying 4-ethylpiperazine (3a–3f) structure were found to be more effective than the compounds carrying 4-methoxyphenyl piperazine (3g–3l) derivatives. Especially, compound 3f bearing the nitro substituent was found to be the most promising compound on BChE in the series. The absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were predicted by using the SwissADME server. The potential binding mode and stability of compound 3f with BChE were investigated by the molecular docking and dynamics simulations. The results showed that 3f was strongly bound up with BChE with the optimal conformation; in addition, their binding free energy reached −167.936 ± 13.109 kJ/mol.
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- 2022
36. Design, synthesis and molecular docking studies of novel benzimidazole-1,3,4-oxadiazole hybrids for their carbonic anhydrase inhibitory and antioxidant effects
- Author
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Kaan Küçükoğlu, Ulviye Acar Çevik, Hayrunnisa Nadaroglu, Ismail Celik, Ayşen Işık, Hayrani Eren Bostancı, Yusuf Özkay, Zafer Asım Kaplancıklı, and Eczacılık Fakültesi
- Subjects
Organic Chemistry ,Benzimidazole ● 1,3,4-Oxadiazole ● Carbonic anhydrase ● Molecular Docking ● Antioxidant ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.In this study, eleven new compounds with a series of benzimidazole-1,3,4-oxadiazole derivatives structures were synthesized and evaluated for their human (h) carbonic anhydrase inhibitory activities against two isoforms hCA I, hCA II, and antioxidant activity. The synthesized compounds were fully characterized by spectral analysis methods such as 1H-NMR, 13C-NMR, and HRMS. Compared to acetazolamide (IC50 = 2.26 µM) for hCA I, the most potent compound 4a was with the IC50 value of 1.322 µM and compound 4d is the other molecule with a greater IC50 value (IC50 = 1.989 µM) than that of acetazolamide in these series. Among all the compounds, 4a (1.826 µM), 4d (1.502 µM), and 4g (1.886 µM) are the most active hybrids against carbonic hCA II. Considering that compound 4a containing 4-bromophenyl structure is effective on both hCA I and hCA II, it can be considered as a promising structure for the development of effective candidates with potent CA inhibitory activities. TAS assay was used to evaluate the antioxidant activities of synthesized compounds. The synthesized compound was analyzed for their in vitro cytotoxic activity on the L929 cell line by using MTT assay. In the last step of this study, molecular docking studies were performed in order to compare the biological activities of the most active molecules against the enzymes of hCAI and hCA II.
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- 2022
37. Synthesis and Molecular Docking of New N-Acyl Hydrazones-Benzimidazole as hCA I and II Inhibitors
- Author
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Ulviye Acar Çevik, Kaan Küçükoğlu, Hayrunnisa Nadaroglu, Ismail Celik, Ayşen Işık, Hayrani Eren Bostancı, Yusuf Özkay, and Zafer Asım Kaplancıklı
- Subjects
Drug Discovery - Abstract
Background: The carbonic anhydrases (CAs) which are found in most living organisms is a member of the zinc-containing metalloenzyme family. The abnormal levels and activities are frequently associated with various diseases therefore CAs have become an attractive target for the design of inhibitors or activators that can be used in the treatment of those diseases. Methods: Herein, we have designed and synthesized new benzimidazole-hydrazone derivatives to investigate the effects of these synthesized compounds on CA isoenzymes. Chemical structures of synthesized compounds were confirmed by 1H NMR, 13C NMR, and HRMS. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase I and II by in vitro assay. Results: These compounds have IC50 values of 5.156-1.684 μM (hCA I) and 4.334-2.188 μM (hCA II). Inhibition types and Ki values of the compounds were determined. The Ki values of the compounds were 5.44 ± 0.14 μM-0.299 ± 0.01 μM (hCA I) and 3.699 ± 0.041 μM-1.507 ± 0.01 μM (hCA II). The synthetic compounds displayed inhibitory action comparable to that of the clinically utilized reference substance, acetazolamide. According to this, compound 3p was the most effective molecule with an IC50 value of 1.684 μM. Accordingly, the type of inhibition was noncompetitive and the Ki value was 0.299 ± 0.01 μM. Conclusion: According to the in vitro test results, detailed protein-ligand interactions of the compound 3p, which is more active against hCA I than standard azithromycin (AZM), were analyzed. In addition, the cytotoxic effects of the compounds on the L929 healthy cell line were evaluated.
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- 2022
38. YENİ BENZİMİDAZOL-HİDRAZON TÜREVLERİNİN TASARIMI, SENTEZİ VE KOLİNESTERAZ İNHİBİTÖR AKTİVİTESİ
- Author
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Ulviye Acar Çevik and Begüm Nurpelin Sağlık
- Subjects
chemistry.chemical_classification ,Benzimidazole ,Farmakoloji ve Eczacılık ,Stereochemistry ,Benzimidazol,Hidrazon,Asetilkolinesteraz,Butirilkolinesteraz ,Hydrazone ,Acetylcholinesterase ,chemistry.chemical_compound ,chemistry ,Acetylcholinesterase,benzimidazole,butyrylcholinesterase,hydrazone ,General Earth and Planetary Sciences ,Pharmacology and Pharmacy ,Butyrylcholinesterase ,General Environmental Science - Abstract
Inadequate cholinergic transmission plays an important role in the development of cognitive, functional, and behavioral symptoms in Alzheimer's disease. Therefore, treatments are generally planned to increase the function of the cholinergic system either with receptor agonist or acetylcholinesterase inhibitors (AChEI). In this study, seven original benzimidazole-hydrazone derivative compounds were synthesized, and acetylcholinesterase (AChE) and butyrylcholine esterase (BuChE) inhibition activities were evaluated. The chemical structures of the synthesized compounds were illuminated with 1H-NMR and LCMS-IT-TOF data. The spectrophotometric Ellman method was used to evaluate AChE and BuChE inhibitory activities of the synthesized compounds. Compound 4g (2-(4-ethoxyphenyl)-N'-(4-(morpholin-1-yl)-benzylidene)-1H-benzo[d]imidazole-6-carbohydrazid) with the highest AChE inhibitory activity from the synthesized compounds while showing this compound showed low activity on BuChE. Significant AChE inhibitory activity was also observed in compound 4c (2-(4-ethoxyphenyl) -N'-(4-(4-methyl-piperidin-1-yl)-benzylidene)-1H-benzo[d]imidazole-6-carbohydrazide and compound 4e (2-(4-ethoxyphenyl)-N'-(4-(4-methyl-piperazin-1-yl)-benzylidene)-1H-benzo[d]imidazole-6-carbohydrazide) derivatives. Consequently, this study presents important results for developing new agents for neurodegenerative diseases such as Alzheimer’s diseases., Yetersiz kolinerjik transmisyon, Alzheimer hastalığında bilişsel, işlevsel ve davranışsal belirtilerin ortaya çıkmasında önemli bir rol oynamaktadır. Dolayısıyla, tedaviler genellikle ya reseptör agonisti ya da asetilkolinesteraz inhibitörleri (AChEI) ile kolinerjik sistemin işlevini arttırmaya yönelik planlanmaktadır. Bu çalışmada, yedi orijinal benzimidazol-hidrazon türevi bileşik sentezlenmiş ve bu bileşiklerin asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) inhibisyon aktiviteleri değerlendirilmiştir. Sentezlenen bileşiklerin kimyasal yapıları, 1H-NMR ve LCMS-IT-TOF verileri ile aydınlatılmıştır. Sentezi gerçekleştirilen bileşiklerin AChE ve BuChE inhibitör aktivitelerinin değerlendirilmesinde spektrofotometrik Ellman yöntemi kullanılmıştır. Sentezlenen bileşiklerden en yüksek AChE inhibitör aktiviteyi 96±3,37 nMIC50 değeri ile bileşik 4g (2-(4-etoksifenil)-N’-(4-(morfolin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) gösterirken, bu bileşik Bu ChE üzerinde düşük aktivite göstermiştir. Bileşik 4c (2-(4-etoksifenil)-N’-(4-(4-metil-piperidin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) ve bileşik 4e (2-(4-etoksifenil)-N’-(4-(4-metil-piperazin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) türevlerinde de belirgin AChE inhibitör aktivite gözlenmiştir.Sonuç olarak, bu çalışma Alzheimer hastalıkları gibi nörodejeneratif hastalıklar için yeni ajanlar geliştirmek için önemli sonuçlar sunmaktadır.Yetersiz kolinerjik transmisyon, Alzhemier hastalığında bilişsel, işlevsel ve davranışsal belirtilerin ortaya çıkmasında önemli bir rol oynamaktadır. Dolayısıyla, tedaviler genellikle ya reseptör agonisti ya da asetilkolinesteraz inhibitörleri (AChEI) ile kolinerjik sistemin işlevini arttırmaya yönelik planlanmaktadır. Bu çalışmada, yedi orijinal benzimidazol-hidrazon türevi bileşik sentezlenmiş ve bu bileşiklerin asetilkolinesteraz (AChE) ve butirilkolin esteraz (BuChE) inhibisyon aktiviteleri değerlendirilmiştir. Sentezlenen bileşiklerin kimyasal yapıları, 1H-NMR ve LCMS-IT-TOF verileri ile aydınlatılmıştır. Sentezi gerçekleştirilen bileşiklerin AChE ve BuChE inhibitör aktivitelerinin değerlendirilmesinde spektrofotometrik Ellman yöntemi kullanılmıştır. Sentezlenen bileşiklerden en yüksek AChE inhibitör aktiviteyi 0.096±0.003 IC50 değeri ile bileşik 4g (2-(4-Etoksifenil)-N’-(4-(morfolin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) gösterirken, bu bileşik BuChE üzerinde düşük aktivite göstermiştir. Bileşik 4c (2-(4-Etoksifenil)-N’-(4-(4-metil-piperidin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) ve bileşik 4e (2-(4-Etoksifenil)-N’-(4-(4-metil-piperazin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) türevlerinde de belirgin AChE inhibitör aktivite gözlenmiştir.
- Published
- 2020
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39. Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors
- Author
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Begüm Nurpelin Sağlık, Zafer Asım Kaplancıklı, Betül Kaya Çavuşoğlu, Derya Osmaniye, Serkan Levent, Ahmet Mücahit Şen, Ulviye Acar Çevik, Abdullah Burak Karaduman, Yusuf Özkay, and Asaf Evrim Evren
- Subjects
Models, Molecular ,Benzimidazole ,Cell Survival ,medicine.drug_class ,In silico ,Molecular Conformation ,Antineoplastic Agents ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Aromatase ,Catalytic Domain ,medicine ,Humans ,MTT assay ,IC50 ,Cell Proliferation ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,Aromatase Inhibitors ,010405 organic chemistry ,Chemistry ,Active site ,0104 chemical sciences ,Molecular Docking Simulation ,Enzyme ,Biochemistry ,A549 Cells ,Estrogen ,MCF-7 Cells ,biology.protein ,Benzimidazoles ,Cisplatin - Abstract
Inhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.
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- 2020
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40. Synthesis, molecular modeling, quantum mechanical calculations and ADME estimation studies of benzimidazole-oxadiazole derivatives as potent antifungal agents
- Author
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Ulviye Acar Çevik, Ismail Celik, Ayşen Işık, Renjith Raveendran Pillai, Trina Ekawati Tallei, Rohitash Yadav, Yusuf Özkay, and Zafer Asım Kaplancıklı
- Subjects
Inorganic Chemistry ,Organic Chemistry ,Spectroscopy ,Analytical Chemistry - Abstract
© 2021In this study, a series of new 3-((5-(4-(5-substitue-1H-benz[d]imidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio)-1-phenyl propane-1-on (4a-4d) derivatives has been designed and synthesized as probable antifungal agents. The final compounds were screened for antifungal activity against Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019) and Candida albicans (ATCC 24433) by employing the broth micro-dilution method. All the new compounds’ structures were elucidated by 1H NMR, 13C NMR, and MS spectral data analysis results. The results demonstrated that compounds 4a (MIC50=0,78 µg/mL) and 4b (MIC50=0,78 µg/mL) possessed better inhibitory activity against C. albicans than ketoconazole (MIC50=1,56 µg/mL). Molecular docking studies of compounds were performed at the active site of 14-alpha demethylase and estimated ADME profiles were calculated. Furthermore, 100 ns simulations were carried out of CYP51-4a, CYP51-4b, CYP51-4c, & CYP51-4d, protein-ligand complexes which revealed mean RMSD values are 0.22, 0.28, 0.26, and 0.23 nm, respectively. The simulation result shows lead compounds bound tightly within the cavity of the CYP51 target protein and thus having conformational stability. The simulation and MM/PBSA results reveal that all ligand-protein complexes are stable and have stable interactions till 100 ns simulation time. Thus, these synthesized lead compounds can be further analyzed for in vitro, in vivo experimental validation as antifungal candidates.
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- 2022
41. New imidazole derivatives as aromatase inhibitor: Design, synthesis, biological activity, molecular docking, and computational ADME-Tox studies
- Author
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Gökay Çetiner, Ulviye Acar Çevik, Ismail Celik, Hayrani Eren Bostancı, Yusuf Özkay, and Zafer Asım Kaplancıklı
- Subjects
Inorganic Chemistry ,Organic Chemistry ,Spectroscopy ,Analytical Chemistry - Abstract
In this study, a series of imidazole derivatives was designed, synthesized, and evaluated forin vitrobiological activity on the human breast cancer cell line MCF7 by MTT assay. To determine the selectivity of the compounds, their cytotoxic effects on the L929 (healthy mouse fibroblast) cell line were also investigated. Compounds1a, 1b, and1dwere found to be more effective than the reference drug cisplatin against the MCF7 cell line. It is seen that the cytotoxic effects of the compounds on the L929 cell line are quite low, and the compounds are found to be highly selective. The inhibition potentials of the compounds1a, 1b, 1d, and1kwhich were effective on the MCF7 cell line, and on the aromatase enzyme were evaluated and it was found that the compounds had similar effects to the reference drug letrozole. Further, the interactions between the best active compounds and the human aromatase cytochrome P450 (CYP) enzyme were analyzed through a molecular docking study. The findings suggest that these compounds could be a promising candidate for the creation of a new family of non-steroidal aromatase inhibitors. Finally, computational ADME-Tox studies of compounds1a, 1b, 1d, and1kwere performed and found to have the appropriate profile.
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- 2023
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42. Synthesis, and docking studies of novel tetrazole-S-alkyl derivatives as antimicrobial agents
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Ulviye Acar Çevik, Ismail Celik, Ayşen Işık, Ülküye Dudu Gül, Gizem Bayazıt, Hayrani Eren Bostancı, Yusuf Özkay, Zafer Asım Kaplancıklı, and Eczacılık Fakültesi
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Inorganic Chemistry ,Organic Chemistry ,Tetrazole ,antimicrobial ,candida ,molecular docking ,14a-demethylase ,Biochemistry - Abstract
A series of novel tetrazole-S-alkyl-piperazine derivatives were synthesized and evaluated for their antifungal activity against C. albicans (ATCC 24433), C. krusei (ATCC 6258) and C. parapsilosis (ATCC 22019) and antibacterial activity against E. coli (ATCC 25922), S. marcescens (ATCC 8100), K. pneumoniae (ATCC 13883), P. aeruginosa (ATCC 27853), E. faecalis (ATCC 2942), B. subtilis (ATCC), S. aureus (ATCC 29213), S. epidermidis (ATCC 12228). Among the synthesized compounds, 1-(4-cycylohexylpiperazin-1-yl)-2-((1-methyl-1H-tetrazol-5-yl)thio)ethan-1-one (2b) (MIC = 7.81 µg/mL) and 1-(4-(4-chlorobenzyl)piperazin-1-yl)-2-((1-methyl-1H-tetrazol-5-yl)thio)ethan-1-one (2f) (MIC = 3.90 µg/mL) displayed significant antifungal activity and compared to reference drugs voriconazole and fluconazole. Besides, compound 2b has showed also higher antibacterial activity against E. faecalis (ATCC 2942) as a reference drug azithromycin, with a MIC value of 3.90 µg/mL, and compound 2d was found to be effective against S. epidermidis (ATCC 12228) as the same reference drug, with a MIC value of 7.81 µg/mL. All the derivatives were efficiently synthesized by a two-step process. The structure of the newly synthesized compounds was elucidated by their 1H NMR, 13C NMR, LC-MS/MS, and elemental analysis. In this study, the detailed synthesis, spectroscopic and biological evaluation data are reported. Molecular docking studies of all compounds were performed with the sterol 14-alpha demethylase enzyme of C. albicans, the target enzyme of azole antifungal drugs.
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- 2022
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43. Design, synthesis, molecular modeling, DFT, ADME and biological evaluation studies of some new 1,3,4-oxadiazole linked benzimidazoles as anticancer agents and aromatase inhibitors
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Ulviye Acar Çevik, Ismail Celik, Ayşen Işık, Iqrar Ahmad, Harun Patel, Yusuf Özkay, and Zafer Asım Kaplancıklı
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Structural Biology ,General Medicine ,Molecular Biology - Abstract
Breast cancer is the most frequent female cancer and second cause of cancer-related deaths among women around the world. Two thirds of breast cancer patients have hormone-dependent tumors, which is very likely be treated with hormonal therapy. Aromatase is involved in the biosynthesis of estrogen thus a critical target for breast cancer. In this study, in order to identify new aromatase enzyme inhibitors, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5.165 ± 0.211 μM and 5.995 ± 0.264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking and dynamics simulations against aromatase enzyme was performed to determine possible protein-ligand interactions and stability. DFT study was performed to evaluate the quantum mechanical and electronic properties of compound 5a. Finally, the theoretical ADME properties of the potential aromatase inhibitor compound 5a were analyzed by calculations. Communicated by Ramaswamy H. Sarma
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- 2022
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44. Synthesis, characterization, molecular docking, dynamics simulations, and
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Ayşen, Işık, Ulviye Acar, Çevik, Ismail, Celik, Tuğba, Erçetin, Ahmet, Koçak, Yusuf, Özkay, and Zafer Asım, Kaplancıklı
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Molecular Docking Simulation ,Structure-Activity Relationship ,Molecular Structure ,Butyrylcholinesterase ,Acetylcholinesterase ,Cholinesterase Inhibitors - Abstract
In this study, two novel series of thiazolylhydrazone derivatives containing 4-ethylpiperazine (
- Published
- 2021
45. Yeni Tiyazolil-Hidrazin Türevlerinin Sentezi ve Asetilkolinesteraz (AChE) ve Bütirilkolinesteraz (BuChE) Aktivite Çalışmaları
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Ayşen IŞIK, Ulviye ACAR ÇEVİK, Tugba ERCETİN, and Ahmet KOÇAK
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Basic Sciences ,Temel Bilimler ,Alzheimer Hastalığı,Tiyazolilhidrazin,Ellman Metot ,General Medicine ,Alzheimer,Thiazolylhydrazine,Ellman Method - Abstract
Alzheimer's disease (AD) has been associated with ecreased cognitive function, memory loss, and dementia due to the death of brain cells over time. Existence of limiting practices in the treatment of AD, and the fact that the disease ranks third in health expenditures in the world after cancer and heart diseases, directs researchers to early diagnosis and new treatment methods on AD. Today, it is thought that there is a direct relationship between cholinergic abnormalities and AD. Studies have shown that acetylcholine (ACh) level increases due to acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition can improve cognitive impairment in the initial stages of Alzheimer's disease. The best method to increase these ACh levels is to suppress the AChE or BuChE enzymes that break down ACh. Therefore, in this study, substituted thiazolylhydrazine derivatives were designed, synthesized and their cholinesterase inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes against AD were investigated. The structures of the target compounds were illuminated by 1H NMR/13C NMR analysis methods. The effects of the target compounds on the on AChE and BuChE enzymes were evaluated using the Ellman process and as a result of the enzyme inhibiton studies of the target compounds, it was determined that the 3d compound showed moderate butyrylcholinesterase activity., Alzheimer hastalığı (AH), zamanla beyin hücrelerinin ölümüne bağlı olarak bilişsel işlevlerde azalma, hafıza kaybı ve bunama ile ilişkilendirilmiştir. Alzheimer hastalığının tedavisinde sınırlayıcı uygulamaların mevcut oluşu, hastalığın sağlık harcamalarında kanser ve kalp hastalıklardan sonra dünyada üçüncü sırada oluşu araştırmacıları AH üzerinde erken evrede tanıma ve yeni tedavi yöntemlerine yönlendirmektedir. Günümüzde kolinerjik anomalikler ile AH arasında doğrudan bir ilişki olduğu düşünülmektedir. Çalışmalar, asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) inhibisyonunun asetilkolin (ACh) seviyesinde meydana gelen artışların Alzheimer hastalığının başlangıç evrelerindeki bilişsel yetmezliği iyileştirebileceğini kanıtlamıştır. Dolayısıyla ACh düzeylerini arttırmak için uygulanacak en iyi metot ise, ACh’yi yıkan AChE veya BuChE enzimlerinin baskılanmasıdır. Dolayısıyla yapılan bu çalışmada, sübstitüe edilmiş tiyazolilhidrazin türevleri tasarlanmış, sentezlenmiş ve AH’ ye karşı asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) kolinesteraz enzimlerinin inhibisyon potansiyelleri araştırılmıştır. Hedef bileşiklerin yapıları 1H NMR/13C NMR analiz yöntemleri ile aydınlatılmıştır. Hedef bileşiklerin AChE ve BuChE enzimleri üzerindeki inhibisyon etkileri Ellman yöntemiile değerlendirilmiş ve hedef bileşiklerin enzim inhibisyon çalışmaları sonucunda 3d bileşiğinin orta düzeyde bütirilkolinesteraz enzimini inhibe ettiği tespit edilmiştir.
- Published
- 2021
46. Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors
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Ulviye Acar Çevik, Zafer Asım Kaplancıklı, Yusuf Özkay, Ayşen Işık, and Ismail Celik
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chemistry.chemical_compound ,chemistry ,Design synthesis ,biology ,biology.protein ,Oxadiazole ,Aromatase ,Combinatorial chemistry ,Biological evaluation ,ADME - Abstract
In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.
- Published
- 2021
- Full Text
- View/download PDF
47. Novel 1,3,4-thiadiazole compounds as potential MAO-A inhibitors – design, synthesis, biological evaluation and molecular modelling
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Begüm Nurpelin Sağlık, Zafer Asım Kaplancıklı, Yusuf Özkay, Derya Osmaniye, Serkan Levent, Ulviye Acar Çevik, and Betül Kaya Çavuşoğlu
- Subjects
Drug ,media_common.quotation_subject ,Pharmaceutical Science ,01 natural sciences ,Biochemistry ,Pharmacokinetics ,Clorgyline ,Drug Discovery ,Moclobemide ,medicine ,IC50 ,Alkyl ,media_common ,Pharmacology ,chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Combinatorial chemistry ,0104 chemical sciences ,Chemistry ,010404 medicinal & biomolecular chemistry ,Monoamine neurotransmitter ,chemistry ,Molecular Medicine ,Selectivity ,medicine.drug - Abstract
Monoamine oxidases (MAOs) are important drug targets for the management of neurological disorders. Herein, a series of new 1,3,4-thiadiazole derivatives bearing various alkyl/arylamine moieties as MAO inhibitors were designed and synthesized. All of the compounds were more selective against hMAO-A than hMAO-B. The half maximal inhibitory concentration (IC(50)) values of most of the compounds were lower than that of the common drug moclobemide (IC(50) = 4.664 μM) and compound 6b was proven to be the most active compound (IC(50) = 0.060 μM). Moreover, it was seen that compound 6b showed a similar inhibition profile to that of clorgyline (IC(50) = 0.048 μM). The inhibition profile was found to be reversible and competitive for compound 6b with MAO-A selectivity. Molecular modelling studies aided in the understanding of the interaction modes between compound 6b and MAO-A. Furthermore, this compound was predicted to have a good pharmacokinetic profile and high BBB penetration. Therefore, such compounds are of interest towards developing new MAO inhibitors.
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- 2020
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48. Antikanser Ajanlar İçin Hedef Olarak DNA Topoizomerazlar
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Ulviye Acar Çevik
- Subjects
General Engineering - Published
- 2020
- Full Text
- View/download PDF
49. Yeni 1,3,4-Tiyadiazol-Piperazin Türevlerinin Sentezi, İn Vitro Antikolinesteraz ve Antimikrobiyal Değerlendirilmesi
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Begüm Nurpelin Sağlik and Ulviye Acar Çevik
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Piperazine ,chemistry.chemical_compound ,1,3,4-Thiadiazole,Antimicrobial,Anticholinesterase,Piperazine ,Engineering ,chemistry ,Thiadiazole,Antimicrobial,Anticholinesterase,Piperazine ,Mühendislik ,General Medicine ,Antimicrobial ,Molecular biology ,In vitro - Abstract
In this study, 8 new compounds having 2-((5-substituted-1,3,4-thiadazol-2-yl)amino)-2-oxoethyl-4- substituepiperazine-1-carbodithioate structures were synthesized, antimicrobial and anticholinesterase activities were evaluated. The structures of synthesized compounds were proved by 1H NMR, 13C NMR and mass spectra. The synthesized compounds were tested for antibacterial activity against eight bacteria strains and antifungal activity against four fungus strains. When the antibacterial activities of the compounds were examined, it was found that the compounds 3c, 3d, 3g and 3h were effective against E. faecalis (ATCC 29212) and E. faecalis (ATCC 51922) with MIC value of 25 µg/mL. It was determined that the carbon chain at the para position of piperazine increased the activity but where as the addition of benzyl group to the para position (3a, 3b, 3e, 3f) did not affect the activity. Furthermore, the acetylcholinesterase activity of the synthesized compounds was examined but none of the compounds showed AChE inhibitory activity as much as standard drug Donepezil., Bu çalışmada2-((5-substitüe-1,3,4-tiyadiazl-2-il)amino)-2-oksoetil-4- substituepiperazin-1-karboditiyatyapısında 8 yeni bileşiğin sentezi yapılarak, antimikrobiyal veantikolinesteraz aktiviteleri incelenmiştir. Sentezlenen bileşiklerin yapıları 1H-NMR,13 C-NMR ve kütle spektrumları kullanılarak kanıtlanmıştır. Aktivitesonuçları incelendiğinde, çoğu bileşiğin S. aureus (ATCC 25923), E.fecalis (ATCC 29212), E. fecalis (ATCC 51922), L. monocytogenes(ATCC 1911), K. pneumoniae (ATCC 700603), P. aeruginosa (ATCC27853), E.coli (ATCC 35218), E. coli (ATCC 25923), C. albicans(ATCC 90028), C. glabrata (ATCC 90030), C. krusei (ATCC 6258), C. parapsilopsis (ATCC 22019)karşı standart bileşikler olan kloramfenikol ve ketakonazol kadar etkiliolmadıkları görülmüştür. Bileşiklerin antibakteriyel aktiviteleriincelendiğinde 3c, 3d, 3g ve 3h kodlu bileşiklerin diğer bileşiklere göre dahayüksek aktiviteye sahip olduğu görülmüştür. Piperazinin para konumunda bulunankarbon zincirinin aktiviteyi arttırdığı (3c, 3d, 3g, 3h), ancak para konumuna benzil grubunun eklenmesinin (3a, 3b, 3e, 3f) aktiviteyi etkilemediğibelirlenmiştir. Ayrıca, sentezlenen bileşiklerin asetilkolinesteraz aktivitesiincelenmiş ancak bileşiklerden hiçbiri standart ilaç Donepezil kadar AChEinhibe edici aktivite göstermemiştir.
- Published
- 2019
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50. Synthesis of novel benzimidazole–oxadiazole derivatives as potent anticancer activity
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Nafiz Öncü Can, Zafer Asım Kaplancıklı, Derya Osmaniye, Sinem Ilgın, Yusuf Özkay, Serkan Levent, Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Ulviye Acar Çevik, and Anadolu Üniversitesi
- Subjects
Cisplatin ,4-Oxadiazole ,biology ,Topoisomerase ,Organic Chemistry ,DNA flow cytometric ,Benzimidazole ,chemistry.chemical_compound ,Anticancer ,chemistry ,Biochemistry ,Cell culture ,Apoptosis ,Agarose gel electrophoresis ,medicine ,biology.protein ,DNA supercoil ,2D NMR ,General Pharmacology, Toxicology and Pharmaceutics ,Cytotoxicity ,DNA ,medicine.drug - Abstract
WOS: 000489544600002, DNA topoisomerase I regulates DNA topological structure in many cellular metabolic processes and is a validated target for the development of antitumor agents. in this work, a series of novel 2-[(5-(4-(5(6)-substituted-1H-benzimidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-substitutedphenyl)ethan-1-ones (4a-4s) derivatives have been synthesized and evaluated for DNA Topo I inhibition and cytotoxicity. the structures of the compounds (4a-4s) were confirmed by IR, H-1-NMR, C-13-NMR, 2D NMR, and mass spectroscopy. Anticancer activity of these compounds was assessed against two different human cancer cell lines A549 (human lung adenocarcinoma) and HepG2 (human liver cancer cell line), as well as normal mouse embryonic fibroblast cells (NIH3T3). IC50 values of compounds 4a, 4c, and 4f were highest than those exhibited for the reference drug cisplatin. Then, the inhibitory effect of 4a, 4c, and 4f compounds on topoisomerase I enzyme with the relaxation assay was investigated on supercoiled DNA using agarose gel electrophoresis. the Annexin V-FITC assay demonstrated that these compounds induce cell death by apoptosis., Anadolu University Scientific Research Projects CommissionAnadolu University [1602S065], This study was financially supported by Anadolu University Scientific Research Projects Commission, Project no. 1602S065.
- Published
- 2019
- Full Text
- View/download PDF
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