Sürdürülebilir Kalkınma Amaçları
Yazarlar
- Topal, Fevzi(3)
- Topal, Meryem(3)
- Akocak, Suleyman(2)
- Beydemir, Sukru(2)
- Durgun, Mustafa(2)
- Isik, Mesut(2)
- Koçyigit, Umit Muhammet(2)
- Lolak, Nebih(2)
- Akgul, Bengusu Hacer(1)
- Akyıldız, Esma(1)
- Aydemir, Eda(1)
- Beydemir, Şükrü(1)
- Camadan, Yasemin(1)
- Cetiz, Mehmet Veysi(1)
- Danis, Ozkan(1)
- Gulcin, Ilhami(1)
- Gómez-Torres, Marina(1)
- Işık, Mesut(1)
- Kaya, Afşin Ahmet(1)
- Kaya, Elif Çelenk(1)
- Kırboğa, Kevser Kübra(1)
- Llorent-Martínez, Eulogio J.(1)
- Nar, Merve(1)
- Saka, Enver(1)
- Saral Sarıyer, Ayşegül(1)
- Sariyer, Emrah(1)
- Sarıyer, Emrah(1)
- Senturk, Murat(1)
- Turgut-Balik, Dilek(1)
- Türkes, Cueneyt(1)
- Türkes, Cuneyt(1)
- Yagi, Sakina(1)
- Yakarsonmez, Sinem(1)
- Yapici, Ismail(1)
- Yildiztugay, Evren(1)
- Zengin, Gokhan(1)
- Çevik, Ulviye Acar(1)
- Özad Düzgün, Azer(1)
- Öztürkkan, Füreya Elif(1)
- Ünver, Hakan(1)
Yayınlar
- MakaleAçık Erişim2027Scopus SJRQ2Design, 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.
- MakaleYalnız künye2026Scopus SJRQ3Nicotinamide complexes of metal(II) furan-2-carboxylates: synthesis, determination of crystal structures, Hirshfeld surface analysis, and in vitro and in silico evaluation of inhibitory properties on CA I, CA II, AChE, BChE, and GR enzymes
Nar, Merve; Senturk, Murat; Kaya, Afşin Ahmet; Öztürkkan, Füreya Elif; Kaya, Elif Çelenk; Şahin, Ertan
In this study, nicotinamide complexes of Cu2⁺, Co2⁺, and Zn2⁺ furan-2-carboxylates were synthesized, and the crystal structures of the complexes were characterized by single crystal X-ray diffraction. The chemical composition and functional groups of the complexes were confirmed using elemental analysis, Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible region (UV–Vis) spectroscopy, and mass spectrometry (MS). Hirshfeld surface analysis detailed the intermolecular interactions present in the crystal structures of the complexes. The complexes feature a central six-coordinate ion (Cu2⁺, Co2⁺, or Zn2⁺) located on an inversion center, which is bonded to two N atoms from nicotinamide and four O atoms from water molecules. There is a furan 2-carboxylate anion that is not coordinated with metal atoms but links to complex structures via hydrogen bonds. Within the scope of biochemical studies, the inhibitory effects of the synthesized complexes on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase I and II (hCA I, hCA II), and glutathione reductase (GR) enzymes were investigated by spectrophotometric methods. It was determined that the complexes, especially Complex 2, exhibited strong enzyme inhibition properties. Molecular docking analyses revealed the binding tendencies and binding energies of the complexes to the active sites of the enzymes. Complex 2 has a high binding affinity with AChE, BChE, hCA I, hCA II, and GR enzymes, and these bindings were supported by hydrogen bonds and π-π interactions. ADMET predictions showed that the complexes have toxicologically safe profiles despite their pharmacokinetic limitations, such as low gastrointestinal absorption and inability to cross the blood–brain barrier. It was determined that the risks of hepatotoxicity, carcinogenicity, immunotoxicity, and mutagenicity were low. As a result, these metal complexes are evaluated as potential therapeutic agents in the treatment of diseases such as Alzheimer’s disease, glaucoma, epilepsy, malaria, and cancer. The data obtained in this study emphasize the biological activities and pharmacological potential of the complexes, and it is recommended that they be supported by future in vivo studies.
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İncele - MakaleAçık Erişim2026Scopus SJRQ2Chemical Constituents and Biological Potentials of Teucrium scordium subsp. scordioides Extracts: In Vitro Experimental and In Silico Perspectives
Akgul, Bengusu Hacer; Yagi, Sakina; Cetiz, Mehmet Veysi; Saka, Enver; Zengin, Gokhan; Llorent-Martínez, Eulogio J.; Gómez-Torres, Marina; Yapici, Ismail; Gulcin, Ilhami; Yildiztugay, Evren
This study was undertaken to examine, for the first time, the antioxidant and enzyme inhibitory properties of several extracts obtained from the aerial parts of Teucrium scordium subsp. scordioides (Schreb.) Arcang (family: Lamiaceae). Among the extracts, the EtOH extract contained the highest total phenolic (89.96 mg GAE/g) and flavonoid (45.74 mg RE/g) contents. Phenylethanoid glycosides were predominant, particularly in the ethanol and aqueous extracts, and teucroside/forsythoside B and verbascoside/forsythoside A were tentatively identified as the major compounds. EtOH and 70% EtOH extracts showed comparable (p > 0.05) anti-DPPH activity (201.89 and 188.52 mg TE/g), Cu++ (562.81 and 547.88 mg TE/g), and Fe+++ (329.13 and 320.08 mg TE/g) reducing capacities. The EtOH extract showed the best antityrosinase activity (72.00 mg KAE/g). The EtOAc extract inhibited human carbonic anhydrase (CA) isoenzymes I and CAII (IC50 = 26.86 and 65.37 mu g/mL, respectively). Complementary in silico analyses of the major phenylethanoid and flavonoid glycosides supported their possible multitarget interaction patterns and identified the Forsythoside A-BChE complex as a computationally favorable model for future experimental validation. Overall, these findings indicate that T. scordium subsp. scordioides may represent a natural source of antioxidants and enzyme inhibitors for use in different health-promoting formulations.
- MakaleAçık Erişim2025Scopus SJRQ1Sulfonamide-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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İncele - MakaleAçık Erişim2024Scopus SJRQ3Design and Synthesis of Pyrazole Carboxamide Derivatives as Selective Cholinesterase and Carbonic Anhydrase Inhibitors: Molecular Docking and Biological Evaluation
Durgun, Mustafa; Akocak, Suleyman; Lolak, Nebih; Topal, Fevzi; Koçyigit, Umit Muhammet; Türkes, Cueneyt; Isik, Mesut; Beydemir, Sukru
The present study focused on the synthesis and characterization of novel pyrazole carboxamide derivatives (SA1-12). The inhibitory effect of the compounds on cholinesterases (ChEs; AChE and BChE) and carbonic anhydrases (hCAs; hCA I and hCA II) isoenzymes were screened as in vitro. These series compounds have been identified as potential inhibitors with a KI values in the range of 10.69 +/- 1.27-70.87 +/- 8.11 nM for hCA I, 20.01 +/- 3.48-56.63 +/- 6.41 nM for hCA II, 6.60 +/- 0.62-14.15 +/- 1.09 nM for acetylcholinesterase (AChE) and 54.87 +/- 7.76-137.20 +/- 9.61 nM for butyrylcholinesterase (BChE). These compounds have a more effective inhibition effect when compared to the reference compounds. In addition, the potential binding positions of the compounds with high affinity for ChE and hCAs were demonstrated by in silico methods. The results of in silico and in vitro studies support each other. As a result of the present study, the compounds with high inhibitory activity for metabolic enzymes, such as ChE and hCA were designed. The compounds may be potential alternative agents used as selective ChE and hCA inhibitors in the treatment of Alzheimer ' s disease and glaucoma. image
AtıfScopus28WoS28OpenAlex27İncele - MakaleYalnız künye2023Scopus SJRQ3Determination 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.
AtıfScopus11WoS5OpenAlex9İncele - MakaleYalnız künye2022Scopus SJRQ2In vitro and in silico evaluation of some plant extracts and phytocompounds against multidrug-resistant Gram-negative bacteria
Aydemir, Eda; Sarıyer, Emrah; Akyıldız, Esma; Özad Düzgün, Azer; Camadan, Yasemin; Saral Sarıyer, Ayşegül
The spread of multidrug-resistant Gram-negative (MDR) bacteria is a global public health problem, as infections caused by MDR Gram-negative bacteria are difficult to treat. New antibiotic agents need to be developed to overcome this problem, and phytochemicals show promise at this point. In this study, methanol extracts were prepared from cinnamon, thyme, nettle, white tea, rosehip, and antibacterial activity of the methanol extracts was studied against two MDR Gram-Negative bacteria (K. pneumoniae and A. baumannii) by broth microdilution method. The MICs of methanol extracts of cinnamon, rosehip, thyme, white tea for A. baumannii were found as 0.015125 g/ml, 0.07825 g/ml, 0.030625 g/ml, 0.00796875 g/ml, respectively. It was found that only cinnamon methanol extract had antibacterial activity in the used extract concentrations against K. pneumoniae and the MIC value was 0.0605 g/ml. The effects of plant methanol extract with antibacterial activity and imipenem combinations were studied in vitro using the checkerboard method. The FIC Indexes were obtained from the checkerboard results and it was observed that the combination of methanol extract and imipenem showed an antagonistic or additive/indifferent effect but not a synergistic effect. We evaluated the binding affinity of epigallocatechin 3-gallate, quercetin, cinnamaldehyde, carvacrol, and thymol phytocompounds using in silico methods, which are well known as a phytocompounds in white tea, cinnamon, thyme, nettle, and rosehip and have antibacterial activities. The results suggested that these phytocompounds should be supported with in vivo and in vitro experiments to investigate their potential for being inhibitor candidates.
AtıfScopus6WoS4OpenAlex6İncele - MakaleAçık Erişim2018Scopus SJRQ1A study of Bos taurus muscle specific enolase; biochemical characterization, homology modelling and investigation of molecular interaction using molecular docking and dynamics simulations
Sariyer, Emrah; Yakarsonmez, Sinem; Danis, Ozkan; Turgut-Balik, Dilek
Tropical theileriosis caused by Theileria annulata obligate parasite that infect ruminant animals, including Bos taurus. The disease results massive economic losses in livestock production worldwide. Here we describe cloning, expression and both biochemical and structural characterization of beta enolase from Bos taurus in vitro and in silico. The interconversion of 2‑phosphoglycerate to phosphoenolpyruvate was catalyzed by enolase is a metalloenzyme in glycolytic pathway and gluconeogenesis. Enolase from Bos taurus was cloned, expressed and the protein was purified at 95% purity using cobalt column by affinity chromatography. The optimum enzymatic activity was calculated at pH 6.5. For the first time in the literature, the kinetic parameters of the enzyme, Vmax and Km, were measured as 0.1141 mM/min and 0.514 mM, respectively. Besides, Bos taurus enolase 3-dimensional structure was built by homology modelling to be used in silico analyses. The interactions of the enzyme-substrate complex were elucidated by molecular dynamics simulations for 100 ns. These interactions were found to be the same as experimentally determined interactions in yeast. These results would enable further structure based drug design studies with the biochemical characterization of the host organism Bos taurus enolase enzyme in vitro and the elucidation of behavior of enzyme-substrate complex in silico.
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