Sürdürülebilir Kalkınma Amaçları

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• 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.

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  İncele
• MakaleYalnız künye2025Scopus SJRQ3/r/gumushane/13533
  Inhibition Effect of Cordyceps sinensis (C. sinensis) Mycelium on Some Metabolic Enzymes and Investigation of Antioxidant Properties

  Balcı, Neslihan

  Cordyceps sinensis (CS), a traditional medicinal fungus, is a rich source of bioactive metabolites with pharmacological potential. This study investigated the inhibitory effects of CS mycelium on human carbonic anhydrase isoenzymes I and II (hCA I and hCA II) and acetylcholinesterase (AChE), as well as its antioxidant properties. Enzyme inhibition was assessed using spectrophotometric methods, whereas antioxidant capacity was evaluated by DPPH, ABTS, CUPRAC, FRAP, and Fe3⁺-reducing assays. LC-MS/MS analysis identified key secondary metabolites, including apigenin, apigenin-7-glucoside, (+)-taxifolin, dihydrokaempferol, p-coumaric acid, salicylic acid, and L-theanine, with apigenin as the major constituent. CS strongly inhibited hCA I (IC50 = 1.11 µg/mL) and hCA II (IC50 = 1.77 µg/mL), exceeding the potency of acetazolamide, and also showed relevant AChE inhibition (IC50 = 8.00 µg/mL), comparable to tacrine. Antioxidant assays revealed moderate DPPH activity but strong ABTS and CUPRAC reducing capacities, indicating the structural contributions of flavonoids and phenolic acids. These findings suggest that CS possess dual bioactivity through enzyme inhibition and antioxidant effects, highlighting its therapeutic potential against neurodegenerative and oxidative stress–related diseases.

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  İncele
• MakaleAçık Erişim2023Scopus SJRQ3/r/gumushane/14512
  Schiff Base Synthesis with a New Reliable Method and Investigation of Their Inhibition Effects on Glutathione S-Transferase and Cholinesterase Enzymes

  Balcı, Neslihan; Çelik, Hülya; Türkan, Fikret; Çelebioğlu, Neslihan; Çelik, Tuba; Bursal, Ercan

  The principle purpose of this study is to synthesize some Schiff base derivatives with a new microwave irradiation technique and investigate their enzyme inhibition effects. Related Schiff base compounds (1 a–1 h) were synthesized from 4-fluoro aniline and some substituted benzaldehyde derivatives (3 a–3 h). The chemical structures of Schiff bases were elucidated by various spectroscopic methods (1H NMR, 13C NMR). The inhibitory effects of the synthesized compounds against acetylcholinesterase, butyrylcholinesterase and glutathione S-transferase were investigated. The in vitro enzyme study determined the best enzyme inhibitors for AChE, BChE, and GST enzymes as 3 h, 3 b, and 3 e compounds, respectively. The results were compared with the standard drugs tacrine for cholinesterase and ethacrynic acid for GST enzymes. Molecular docking results demonstrated the low binding energy values between −5.8 kcal/mol and −8.7 kcal/mol with hydrogen bonding, hydrophilic, and hydrophobic interactions at the active catalytic sites of the enzymes.

  AtıfScopus14·WoS10·OpenAlex15

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• MakaleYalnız künye2023Scopus SJRQ3/r/gumushane/12751
  Determination of the Antioxidant Capacity of Puerarin and Its Effect on Cholinesterases by in vitro and in silico Methods

  İnan Ergün, Aslı; Topal, Meryem

  Puerarin, which was used as a natural isoflavone in this study, was obtained from the Kudzu plant. The inhibitory effect of puerarin on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes was investigated. The IC50 values of AChE (177.73 nM) and BChE (315.07 nM) were determined. The binding mechanism of puerarin, which has a high inhibitory effect on the active site of the enzyme, was demonstrated by the molecular docking method. The antioxidant activity was evaluated for the same molecule. For this purpose, Fe3+-Fe2+ reducing capacity, ABTS radical scavenging activity, CUPRAC method, DPPH⋅ scavenging activity and DMPD radical scavenging method were used. The percentage (%) inhibition amount of puerarin molecule was calculated as 99.33 % for ABTS radical scavenging activity, which is the more preferred method for natural products. The absorbtion value of iron reduction of Puerarin was 0.122±0.010, and the value of copper reduction was 0.633±0.026. Our research efforts include uncovering the potent antioxidant potential of puerarin and, simultaneously, a comparative study of tacrine, primarily emphasizing its inhibitory effects against AChE and BChE enzymes. The puerarin is expected to be a guide for drug discovery against many problems, especially oxidative cell damage in Alzheimer's disease, mitochondrial dysfunction (MD), cancer, and cardiovascular diseases.

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  AtıfScopus11·WoS5·OpenAlex9

  İncele
• MakaleYalnız künye2021Scopus SJRQ2/r/gumushane/12999
  Determination of Angelica archangelica’s Antioxidant Capacity and Mineral Content

  Topal, Meryem; Ozturk Sarıkaya, S. Beyza; Topal, Fevzi

  The aim of this study was to determine the mineral contents by ICP-MS and the antioxidant capacity of Angelica archangelica plant, which is not well known in the literature. For this purpose, ethyl alcohol extracts of the branches and leaves of the plant; different bioanalytical methods such as reducing capacity by Fe3+−Fe2+ transformation method, Fe3+-TPTZ reducing capacity by FRAP method, Cu2+-Cu+ reducing capacity by CUPRAC method, the ferric ions (Fe2+) chelating activity by using bipyridyl reagent, DPPH (1,1-diphenyl-2-picryl-hydrazyl) free radical, DMPD (N,N-dimethyl-p-phenylenediamine), ABTS (2,2’-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activities, total antioxidant activity determination according to thiocyanate method, total phenolic and total flavonoid activity were used. As standard, BHT, BHA, α-Tocopherol, Trolox were used. A. archangelica branches and leaves demonstrated 88.13 % and 93.90 % inhibition of linoleic acid emulsion peroxidation at 20 mg mL−1 concentration. Also, it was determined that both leaves and branches of A. archangelica plant were dense with P, Mg, Ca and K minerals with ICP-MS device. It is considered that the results of the manuscript will guide the antioxidant studies, medicine, cosmetics, pharmacology and food sector.

  AtıfScopus15·WoS12·OpenAlex14

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