Sürdürülebilir Kalkınma Amaçları

• 6

Yazarlar

• Topal, Fevzi(3)
• Topal, Meryem(2)
• Adem, Şevki(1)
• Akincioğlu, Hülya(1)
• Akocak, Suleyman(1)
• Arslanoglu, Hasan(1)
• Aslan, Osman Nuri(1)
• Aydogmus, Ercan(1)
• Aygül, İmdat(1)
• Balci, Neslihan(1)
• Beydemir, Sukru(1)
• Bozkır, İsa(1)
• Demirdağ, Ramazan(1)
• Durgun, Mustafa(1)
• Gül, Abdulkadir(1)
• Güler, Halil İbrahim(1)
• Gülçin, İlhami(1)
• Isik, Mesut(1)
• Kalay, Erbay(1)
• Kayıkçıoğlu Bozkır, İlknur(1)
• Koçyigit, Umit Muhammet(1)
• Kuzu, Müslüm(1)
• Lolak, Nebih(1)
• Sağlamtaş, Rüya(1)
• Türkes, Cuneyt(1)
• Yapar, Gonul(1)
• Yilmaz, Firat(1)
• Yilmaz, Fırat(1)
• Çomaklı, Veysel(1)
• Özgen, Inanc(1)
• Öztürk, Cansu(1)
• İbişoğlu, Merve Seda(1)

• MakaleAçık Erişim2026Scopus SJRQ2/r/gumushane/12191
  Computational prioritization of multi-target inhibitors: explainable QSAR and docking-based discovery of dual AChE/BACE1 chemotypes

  Bozkır, İsa; İbişoğlu, Merve Seda; Kayıkçıoğlu Bozkır, İlknur; Güler, Halil İbrahim

  The discovery of dual acetylcholinesterase (AChE) and β-secretase (BACE1) inhibitors remains a promising strategy against multifactorial Alzheimer’s disease. Here, rigorously curated ChEMBL-derived data were used to develop explainable QSAR (Quantitative structure–activity relationship) models for dual-inhibition prioritization. Molecules were standardized, near-duplicates were removed using a Tanimoto similarity threshold (≥ 0.80), and physicochemical outliers were filtered prior to modeling. Multiple classifiers (including Light Gradient-Boosting Machine, eXtreme Gradient Boosting, Random Forest, Support Vector Machine, k-Nearest Neighbors and Gradient Boosting Decision Trees) and fingerprints (e.g., RDKit fingerprints, Extended Connectivity Fingerprint) were benchmarked under scaffold-based nested cross-validation to prevent data leakage. Class imbalance was handled with SMOTETomek applied strictly within training folds. Model selection relied on F-Score, Area Under the Precision–Recall Curve, Matthews Correlation Coefficient (MCC), and Recall, and performance was accompanied by bootstrap confidence intervals, calibration curves, and Y-randomization controls. In classification, the top model (GBDT + ECFP6) achieved strong generalization (Recall ≈ 1.00, PR-AUC ≈ 0.84, MCC ≈ 0.81, F1 Score ≈ 0.84). Shapley Additive Explanations (SHAP) analysis highlighted aromatic and hydrogen-bonding substructures as key positive contributors. Prospective candidates (e.g., CHEMBL5082250, CHEMBL1651126, CHEMBL1651127) were evaluated by active-site-focused docking against AChE (PDB: 4EY7) and BACE1 (PDB: 2G94) with essential waters retained; docking scores (ΔG, kcal·mol⁻1) were used for relative ranking of the ligands. SwissADME/pkCSM profiling suggested CNS-relevant properties (e.g., MPO, logBB, P-gp liability) and acceptable oral drug-likeness. Collectively, the workflow provides a reproducible and transparent pipeline for prioritizing dual AChE/BACE1 chemotypes and nominates testable scaffolds for experimental validation.

  • 
  AtıfScopus2·WoS2·OpenAlex5

  İncele
• MakaleAçık Erişim2026Scopus SJRQ3/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.

  • 
  İncele
• MakaleAçık Erişim2026Scopus SJRQ2/r/gumushane/10552
  In Vitro Antioxidant, Antibacterial, and Cholinesterase-Inhibitory Properties of an AqueousEuphorbia macrocladaRoot Extract Obtained by Ultrasound-Assisted Extraction

  Gül, Abdulkadir; Yilmaz, Firat; Topal, Fevzi; Özgen, Inanc; Aydogmus, Ercan; Arslanoglu, Hasan

  In the present study, the aqueous extract obtained from the roots of Euphorbia macroclada via ultrasound-assisted extraction (Ult-ER) was evaluated for its anticholinesterase (AChE and BChE), antioxidant, and antibacterial activities. While the extract exhibited weak inhibition against AChE (IC50: 507.69 +/- 17.95 mg/mL), it showed relatively greater inhibitory activity against BChE (IC50: 22.41 +/- 0.49 mg/mL). In antioxidant assays, Ult-ER exhibited measurable antioxidant responses, with DPPH and ABTS(+) radical-scavenging capacities of 18.33 +/- 0.49 and 119.59 +/- 1.86 mg TE/L, respectively. Its Fe-3(+) and Cu-2(+) reducing capacities were 128.51 +/- 12.57 and 670.33 +/- 11.59 mg TE/L, respectively. The total phenolic and flavonoid contents were 84.80 +/- 3.31 mg GAE/g and 60.67 +/- 2.29 mg QE/g, while the total antioxidant capacity was 9.78 +/- 0.44 mg TE/g and 15.62 +/- 1.85 mg BHAE/g. In the antibacterial evaluation, Ult-ER at the highest tested concentration of 8 mg/mL exhibited inhibitory activity against all tested strains, including Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853, whereas no detectable inhibition was observed at lower concentrations.

  • 
  İncele
• MakaleAçık Erişim2025Scopus SJRQ2/r/gumushane/12209
  Novel Sulfonylhydrazones With Sulfonate Ester Framework: Promising Dual Inhibitors of AChE and hCAs

  Öztürk, Cansu; Balci, Neslihan; Aslan, Osman Nuri; Kalay, Erbay

  Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions of individuals worldwide. Treatment strategies for AD vary depending on cognitive and behavioral symptoms, with cholinergic replacement therapy using acetylcholinesterase (AChE) inhibitors being one of the primary approaches. Recent studies have also identified human carbonic anhydrases (hCAs) as significant therapeutic targets for AD, offering new opportunities for the development of innovative treatments. Carbonic anhydrase inhibitors have been shown to prevent early mitochondrial damage and inhibit H2O2 production, thereby reducing amyloid plaque formation. Building on the promising potential of hydrazones particularly sulfonyl hydrazones as anticholinesterase agents, we synthesized 12 novel chlorine-substituted sulfonyl hydrazone compounds containing aryl sulfonate ester groups. These compounds were evaluated for their inhibitory effects on AChE, hCA I, and hCA II enzymes. The synthesized compounds exhibited low nanomolar inhibitory activity, with Ki values ranging from 9.58 ± 2.22 to 104.04 ± 23.82 nM for AChE, 9.12 ± 2.21 to 477.63 ± 218.52 nM for hCA I, and 17.54 ± 7.74 to 564.62 ± 213.98 nM for hCA II. Notably, compound 6 showed strong inhibitory activity against hCA I (Ki = 9.12 ± 2.21 nM; acetazolamide (AZA) = 26.54 ± 3.11 nM) and hCA II (Ki = 17.54 ± 7.74 nM; AZA = 21.73 ± 2.42 nM), whereas compound 4 exhibited superior AChE inhibition (Ki = 9.58 ± 2.22 nM; TAC = 23.12 ± 2.05 nM). The chemical structures of the synthesized compounds were characterized using advanced spectroscopic techniques, including FT-IR, 1H-NMR, and 13C-NMR spectroscopy.

  • 
  AtıfScopus12·WoS11·OpenAlex9

  İncele
• MakaleYalnız künye2024Scopus SJRQ3/r/gumushane/12764
  Assessment of Anticholinergic and Antidiabetic Properties of Some Natural and Synthetic Molecules: An In Vitro and In Silico Approach

  Çomaklı, Veysel; Aygül, İmdat; Sağlamtaş, Rüya; Kuzu, Müslüm; Demirdağ, Ramazan; Akincioğlu, Hülya; Adem, Şevki; Gülçin, İlhami

  Introduction: This study aimed to determine the in vitro and in silico effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. Background: Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM) are considered the most important diseases of today’s world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, developing drugs with high therapeutic efficacy and better pharmacological profile is important. Objectives: This study sets out to determine the related enzyme inhibitors used in treating AD and T2DM, considered amongst the most important diseases of today’s world. Methods: In the current study, the in vitro and in silico effects of dienestrol, hesperetin, L-thyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and α-glycosidase enzyme activities were investigated. Results: All the molecules showed an inhibitory effect on the enzymes. The IC50 and Ki values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 µM and 0.83 ± 0.195 µM, respectively. In addition, dienestrol, T3, and dobutamine molecules showed a more substantial inhibition effect than tacrine. The dobutamine molecule showed the most substantial inhibition effect for the BChE enzyme, and IC50 and Ki values were determined as 1.83 µM and 0.845 ± 0.143 µM, respectively. The IC50 and Ki values for the hesperetin molecule, which showed the strongest inhibition for the α-glycosidase enzyme, were determined as 13.57 µM and 12.33 ± 2.57 µM, respectively. Conclusion: According to the results obtained, the molecules used in the study may be considered potential inhibitor candidates for AChE, BChE and α-glycosidase.

  • 
  AtıfScopus8·WoS7·OpenAlex8

  İncele
• 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.

  • 
  AtıfScopus1·OpenAlex3·TR Dizin2

  İncele