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Sürdürülebilir Kalkınma Amaçları

• 18

• MakaleAçık Erişim2027/r/gumushane/13442
  Design, Synthesis, and X-ray Characterization of Benzohydrazide Derivatives as Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease: An Experimental and Computational Approach to Biological Activity

  Topal, Fevzi; Ünver, Hakan; Topal, Meryem; Çevik, Ulviye Acar; Kırboğa, Kevser Kübra; Işık, Mesut; Beydemir, Şükrü

  In this study, a series of new benzohydrazide derivatives (1a-i) were synthesized, and characterized as potential cholinesterase inhibitors for use in the treatment of Alzheimer’s disease (AD). The inhibitory activities of the synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated using in vitro and in silico methods. IC50 values for AChE inhibition ranged from 29.50 to 46.21 nM, with compound 1c exhibiting the highest inhibitory potential at an IC50 of 29.50 nM. For the BChE enzyme, the strongest effect was observed with compound 1d at an IC50 of 55 nM. The synthesized derivatives exhibited higher inhibitory potential compared to the reference tacrine (IC50: 58.73 nM for AChE and 187.30 nM for BChE) against cholinesterase enzymes through both competitive and non-competitive inhibition mechanisms. Molecular docking (ΔG: -10.67 to -9.95 kcal/mol for AChE; -9.80 to -8.69 kcal/mol for BChE) and 100 ns molecular dynamics simulations supported the binding affinities and indicated the dynamic stability of the enzyme-inhibitor complexes, in agreement with the experimental inhibition data. In silico ADMET profiling indicated favourable drug-likeness and high predicted gastrointestinal absorption and blood-brain barrier permeability (TPSA 41.46-61.69 A2), and structural alert screening returned no PAINS matches. The findings suggest that these derivatives may serve as promising lead compounds for further investigation as potential cholinesterase inhibitors relevant to AD, pending experimental cytotoxicity evaluation.

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• MakaleAçık Erişim2026/r/gumushane/10625
  Mono- and Bis-Ureido Sulfapyridines as Nanomolar Dual Cholinesterase Inhibitors: Enzyme Kinetics, Molecular Docking, and ADME/Tox Insights

  Yapar, Gonul; Akocak, Suleyman; Lolak, Nebih; Topal, Meryem; Türkes, Cuneyt; Topal, Fevzi; Durgun, Mustafa; Koçyigit, Umit Muhammet; Isik, Mesut; Beydemir, Sukru

  A series of mono- and bis-ureido sulfapyridine derivatives (SP-1-SP-10) were synthesized and evaluated as dual cholinesterase inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All compounds exhibited nanomolar inhibition. The most potent AChE inhibitors were SP-8 (K-i = 5.25 +/- 0.73 nM), SP-9 (5.09 +/- 0.44 nM), and SP-10 (5.74 +/- 0.55 nM), significantly outperforming tacrine (K-i = 105.03 +/- 8.85 nM) under identical conditions. For BChE, SP-9 showed the strongest inhibition (K-i = 26.38 +/- 2.07 nM) compared with tacrine (172.03 +/- 32.42 nM). Kinetic analyses revealed competitive inhibition toward AChE for all derivatives, whereas BChE inhibition displayed both competitive and noncompetitive patterns depending on structural features. Glide XP docking using AChE (PDB: 7XN1) and BChE (PDB: 4BDS), complemented by MM-GBSA binding free energy calculations, supported favorable ligand accommodation within the catalytic pockets and highlighted the importance of aromatic and hydrophobic interactions. In silico ADME/Tox analysis revealed a potency-drug-likeness trade-off: mono-ureido derivatives complied with Lipinski's rule of five and showed high predicted oral absorption, whereas bis-ureido derivatives, despite superior enzymatic potency, exhibited multiple drug-likeness violations. These findings identify the ureido-sulfapyridine scaffold as a potent enzymatic dual cholinesterase inhibitory framework, warranting further structural optimization to improve pharmacokinetic properties.

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• MakaleYalnız künye2026/r/gumushane/10493
  Novel Approach to Synthesis of Diaryl Tacrine Derivatives and Evaluation of Their Inhibitory Effects on Cholinesterase Enzymes

  Topal, Fevzi; Ökten, Salih; Misir, Busra Albayrak; Koçyigit, Umit Muhammet; Derin, Yavuz; Atalay, Vildan Enisoglu; Tutar, Ahmet; Topal, Meryem

  The development of effective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors remains a crucial objective in the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). In this study, a novel synthetic approach was established to prepare a series of diaryl-substituted tacrine derivatives. Initially, brominated aminobenzonitrile was subjected to Suzuki-Miyaura cross-coupling reactions with various aryl boronic acids to yielding diaryl-substituted aminobenzonitriles at yields of 60%-72%. These intermediates were then cyclized with cyclohexanone and cycloheptanone under Friedl & auml;nder conditions using BF3 & centerdot;OEt2 as a catalyst, affording six- and seven-membered diaryl tacrine analogues in yields of 52%-68%. All synthesized compounds were characterized by NMR, IR, and elemental analysis. The inhibitory activities of these compounds (7-16) against AChE and BChE were evaluated, and several analogs demonstrated potent dual-enzyme inhibition at nanomolar concentrations. Notably, compounds 8 and 13 exhibited half maximal inhibitory concentration (IC50) values of 6.848 and 8.545 nmol/L for BChE, respectively, indicating strong potential as selective cholinesterase inhibitors. The structure-activity relationship (SAR) analysis revealed the influence of aryl substituents on the potency and selectivity of enzyme inhibition. Compared to previously reported tacrine derivatives, the newly synthesized analogs exhibited superior inhibitory profiles, indicating their potential as lead compounds for further development in AD therapeutics. [GRAPHICS] .

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• MakaleAçık Erişim2026/r/gumushane/13715
  Synthesis, Characterization, Biological Properties, and Sensor Applications of Novel Thiosemicarbazone Derivatives

  Gezegen, Hayreddin; Özbek, Oguz; Topal, Meryem; Şahin, Hatice; Koçyiğit, Ümit M.

  In this study, novel thiosemicarbazone derivative molecules (5a–j) were synthesized. The characterization of the synthesized molecules was carried out using 1H–, 13C–NMR, FT–IR, and Q–TOF spectroscopic techniques. Then, the inhibitory effect of these compounds was examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The hCA I II, and AChE were efficiently inhibited by synthesized thiosemicarbazone derivatives, with Ki values in the range of 0.293–1.666 µM for hCA I, 0.298–1.332 µM for hCA II, and 52.51–138.63 µM for AChE, respectively. Finally, the sensor properties of the synthesized thiosemicarbazone derivatives were investigated. The newly synthesized thiosemicarbazone derivative molecules exhibited high selectivity towards Pb2+ ions. The sensor prepared with 5a from these molecules had a Nernstian behavior of 28.8 ± 1.5 mV/decade and a low detection limit of 2.86 × 10−6 M in a wide concentration range of 1.0 × 10−1–1.0 × 10−5 M. The newly proposed sensor also had a wide pH working range (5.0–10.0), a very fast response time (5 s), and good reproducibility. The newly fabricated sensors were used as indicator electrodes for the potentiometric titration of Pb2+ ions with ethylenediaminetetraacetic acid (EDTA) and were successfully applied for the determination of Pb2+ ion content in different water samples.

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• MakaleAçık Erişim2026/r/gumushane/12105
  Investigation of the enzyme-inhibitory, antibacterial, and anticancer properties of metal phthalocyanines

  Topal, Meryem; Topal, Fevzi; Yilmaz, Fırat; Bulut Atalay, Esra; Koçyiğit, Ümit Muhammet; Güzel, Emre

  In this study, the enzyme inhibitory, antibacterial, and anticancer activities of a phthalonitrile derivative and its metal phthalocyanines (Pcs; indium, zinc, copper, cobalt, and manganese; 1–6) were investigated. The cobalt and manganese Pcs were synthesized for the first time in this study. The inhibitory activities of the symmetric Pcs, which were expected to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) via their 4-(isopropylbenzyl)oxy substituents through host–guest interactions, were investigated. More selective inhibition of AChE than BChE was observed for these compounds. For AChE, CoPc was identified as the most potent inhibitor (IC50 = 14.81 nM), whereas for BChE, InPc was identified as the most potent inhibitor (IC50 = 56.35 nM). The Ki values indicated that most compounds exhibited competitive inhibition; copper phthalocyanine (CuPc) showed particularly strong inhibition against AChE (Ki = 3.08 nM ± 1.12), whereas the lowest Ki value against BChE was observed for MnPc (Ki = 25.98 ± 1.97 nM). Most compounds exhibited competitive inhibition; however, CuPc showed competitive inhibition toward AChE but a noncompetitive inhibition pattern toward BChE. Dual inhibition of AChE and BChE by these compounds may be promising for addressing cholinergic deficits associated with Alzheimer’s disease. In addition, the acceptability of compounds 1–6 with respect to pharmacological drug-likeness criteria was assessed based on predicted absorption, distribution, metabolism, excretion (ADME) outcomes. In antibacterial tests, varying levels of inhibition were observed against selected bacterial strains. In anticancer assays, all compounds exhibited high cytotoxicity against the MCF-7 breast cancer cell line. Higher antiproliferative activity was observed for CuPc than for the other compounds. Morphological changes were induced in cancer cells by CuPc and MnPc. Overall, these compounds may have potential as enzyme inhibitors and as antibacterial and anticancer agents.

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• MakaleAçık Erişim2025/r/gumushane/10564
  Sulfonamide-Bearing Pyrazolone Derivatives as Multitarget Therapeutic Agents: Design, Synthesis, Characterization, Biological Evaluation, In Silico ADME/T Profiling and Molecular Docking Study

  Lolak, Nebih; Akocak, Suleyman; Topal, Meryem; Koçyigit, Umit Muhammet; Isik, Mesut; Türkes, Cuneyt; Topal, Fevzi; Durgun, Mustafa; Beydemir, Sukru

  The research and design of new inhibitors for the treatment of diseases such as Alzheimer's disease and glaucoma through inhibition of cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and carbonic anhydrase enzymes are among the important targets. Here, a series of novel sulfonamide-bearing pyrazolone derivatives (1a-f and 2a-f) were successfully synthesized and characterized by using spectroscopic and analytical methods. The inhibitory activities of these newly synthesized compounds were evaluated both in vitro and in silico for their effect on carbonic anhydrases (hCA I and hCA II isoenzymes) and ChEs. The in vitro studies showed that these novel compounds demonstrated potential inhibitory activity, with K-I values covering the following ranges: 18.03 +/- 2.86-75.54 +/- 4.91 nM for hCA I, 24.84 +/- 1.57-85.42 +/- 6.60 nM for hCA II, 7.45 +/- 0.98-16.04 +/- 1.60 nM for AChE, and 34.78 +/- 5.88-135.70 +/- 17.39 nM for BChE. Additionally, many of these compounds showed promising inhibitory activity, and some showed higher potency than reference compounds. While the in silico studies have also identified the potential binding positions of these compounds, using the crystal structures of hCA I, II, AChE and BChE receptors. The varying affinities demonstrated by these designed compounds for ChEs and hCA isoenzymes show that these compounds could hold promise as potential alternative agents for selectively inhibiting ChEs and hCAs in the treatment of diseases such as Alzheimer's disease and glaucoma.

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• MakaleAçık Erişim2025/r/gumushane/19647
  Exploring the Antioxidant and Neuroprotective Potential of Muscari armeniacum: Phenolic Profiling and Enzyme Inhibition

  Topal, Fevzi; Menevseoglu, Ahmed; Topal, Meryem; Yilmaz, Firat

  This study aimed to investigate the antioxidant and enzyme inhibitory properties of Muscari armeniacum, a plant native to Türkiye, which is known for its bioactive compound content. Ethanol extracts of Muscari armeniacum were prepared and analyzed using a variety of bioanalytical methods to assess its potential health-promoting properties. The antioxidant capacity was evaluated through Fe³⁺-Fe²⁺ reduction capacity, CUPRAC, DPPH, and ABTS radical scavenging activities. Additionally, the total phenolic and flavonoid contents of the extracts were determined, as these compounds are critical indicators of antioxidant potential. The antioxidant activity of Muscari armeniacum was compared with five standard antioxidants commonly used for benchmarking: BHA, α-tocopherol, BHT, trolox, and ascorbic acid. The extract demonstrated a high flavonoid content (23.24 µg QE/mg extract) and a significant amount of phenolics (14.38 µg GAE/mg extract), with the flavonoid content being particularly noteworthy. In addition to its antioxidant properties, the enzymatic activity assays revealed that the extract significantly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, which are associated with neurodegenerative diseases such as Alzheimer’s. The IC₅₀ values were determined to be 54.14 mg/mL (R² = 0.9695) for AChE and 58.73 mg/mL (R² = 0.9609) for BChE, indicating moderate enzyme inhibition. These results suggest that Muscari armeniacum could serve as a valuable source of bioactive compounds with significant antioxidant and enzyme inhibitory activities. Its potential applications in the treatment of oxidative stress-related diseases and neurodegenerative disorders make it a promising candidate for further pharmacological studies. This research underscores the importance of exploring native plants for their medicinal and therapeutic potential, contributing to the development of alternative treatments for challenging health conditions.

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• MakaleAçık Erişim2025/r/gumushane/14138
  Comprehensive Analysis of the Antioxidant and Enzyme Inhibitory Properties and Phenolic Compounds of Phlomis armeniaca: Potential Applicant in Neurodegenerative Diseases

  Menevseoglu, Ahmed; Yılmaz, Fırat; Topal, Meryem; Topal, Fevzi

  This study investigates the antioxidant and enzyme inhibitory properties of Phlomis armeniaca, a perennial plant native to the eastern and southeastern regions of Turkey. Ethanol extracts of the plant were analyzed using various bioanalytical methods, including Fe3⁺-Fe2⁺ reducing power, Cupric Reducing Antioxidant Capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and 2,2-azinobis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical scavenging activities, as well as total phenolic and flavonoid content assessments. The results showed that P. armeniaca is rich in phenolic (38.75 ± 0.59 µg gallic acid equivalents/mg extract) and flavonoid compounds (39.34 ± 4.08 µg quercetin equivalents/mg extract). The plant demonstrated significant inhibitory effects on acetylcholinesterase (half-maximal inhibitory concentration [IC50]: 45.00 ± 0.48 mg/mL) and butyrylcholinesterase (IC50: 84.51 ± 0.84 mg/mL) enzymes, indicating its potential use in treating neurodegenerative diseases such as Alzheimer's. The study also highlighted P. armeniaca’s high chlorogenic acid, salicylic acid, 4-dihydroxybenzoic acid, and quinic acid contents, supporting its antioxidant capacity. These findings suggest that P. armeniaca could be a valuable natural resource for developing therapeutic agents to manage oxidative stress and related conditions, warranting further pharmacological exploration.

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• MakaleYayıncıda açık erişim2024/r/gumushane/10562
  Novel asymmetric biscarbothioamides as Alzheimer's disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies

  Muglu, Halit; Yakan, Hasan; Erdogan, Musa; Topal, Fevzi; Topal, Meryem; Turkes, Cuneyt; Beydemir, Sukru

  Exploring novel frameworks for treating Alzheimer's disease is an ambitious objective. In this particular context, a range of asymmetric biscarbothioamide derivatives (3a-l) with varying substitutions have been meticulously designed and effectively synthesized. The newly synthesized compounds have all been definitively characterized using established spectroscopic techniques such as 1H-NMR, 13C-NMR, FT-IR, and elemental analysis. In vitro, all the derivatives (3a-l) were evaluated to assess their inhibitory potential against cholinesterase enzymes (acetylcholinesterase, AChE, and butyrylcholinesterase, BChE). The outcomes demonstrated that these derivatives were potent and exhibited selectivity in inhibiting AChE, except for compounds 3b and 3e, which specifically inhibited BChE, showcasing varying degrees of KI values. Significantly, compounds 3j (KIs of 11.91 +/- 2.25 nM for AChE and 77.76 +/- 8.02 nM for BChE) and 3h (KIs of 14.73 +/- 2.30 nM for AChE and 59.54 +/- 6.20 nM for BChE) emerged as the most potent dual inhibitors of AChE and BChE within the series, respectively, with KI constants even lower than those of the standard drug tacrine (KIs of 68.70 +/- 5.39 nM for AChE and 111.60 +/- 10.52 nM for BChE). Furthermore, their potential scavenging activity against DPPH and ABTS radicals was evaluated. To further validate the experimental findings, molecular docking studies were performed in silico to ascertain the binding modes of these compounds with the active pockets of AChE and BChE enzymes. Investigating innovative frameworks for addressing Alzheimer's disease is a challenging goal. In this specific scenario, a selection of asymmetric biscarbothioamide derivatives (3a-l) with different substitutions has been carefully formulated and successfully synthesized.

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• MakaleAçık Erişim2024/r/gumushane/12533
  Exploring the Impacts of Angelica purpurascens Extracts on Anticholinergic, Antidiabetic, Antibacterial Potential, and Antioxidant Capacity

  Topal, Meryem; Topal, Fevzi; Yilmaz, Fırat

  In Kars-Sarıkamış-Soğanlı, Angelica purpurascens (A. purpurascens) emerges as a promising natural antioxidant source. Extracts from its leaves, branches, and flowers underwent thorough bioanalytical assessments. The leaf extract exhibited the highest concentrations of herbal flavonoids (45.22 µg QE/mg extract) and total phenolics (28.96 µg GAE/mg extract). Branch extracts demonstrated significant enzymatic activity against AChE and BChE with IC50 values of 37.26 mg/mL and 9.08 mg/mL respectively. The flower extract displayed notable antibacterial properties. This study sheds light on the therapeutic potential of A. purpurascens ethanol extracts, suggesting benefits for Alzheimer’s, cell damage-induced diseases, and diabetes mellitus. It pioneers new enzymatic and antioxidant insights and contributes to understanding this abundant Türkiye species. A. purpurascens holds promise for pharmaceutical exploration, offering potential solutions for challenging health conditions.

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