Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleAçık Erişim2027Design, 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 künye2026Novel 1,2,4-triazole-based n-mannich derivatives: Synthesis, spectroscopic characterization, cytotoxic, antimicrobial, and enzyme inhibitory activities, and in silico studies
Yılmaz, Yonca; Medetalibeyoğlu, Hilal; Kapancık, Serkan; Tüzün, Burak; Lukšič, Miha; Aslan, Rukiye; Topal, Fevzi; Kocyigit, Umit M.; Yüksek, Haydar; Harmankaya, Ahmet
A series of novel 1,2,4-triazole-based Mannich bases was designed, synthesized, and evaluated for biological and theoretical properties. Schiff base intermediates (C1–6) were prepared by condensing 4-benzoxy-3-methoxybenzaldehyde with various 3-substituted-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones. Mannich reactions with formaldehyde and 2,6-dimethylmorpholine produced six target compounds (D1–6). Structures were confirmed using spectroscopic techniques. Following structural confirmation, the compounds showed significant cytotoxicity against HT-29 and MCF-7 cancer cell lines in MTT assays. Enzyme inhibition studies demonstrated activity against glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH), indicating potential relevance to cancer metabolism. Moderate acetylcholinesterase inhibition was observed, with IC50 values from 56.81 to 182.40 µM. Antimicrobial testing showed that D1, D3, D4, and D5 were active against selected microbial strains, while D2 and D6 were inactive. Density functional theory (DFT) calculations, molecular docking, ADME/T predictions, and molecular mechanics simulations were conducted to complement the experimental findings. These computational analyses indicated favorable binding interactions and pharmacological profiles.In summary, the newly synthesized triazole-based Mannich derivatives represent promising candidates for further pharmacological investigation.
- MakaleAçık Erişim2026Investigation 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.
- MakaleAçık Erişim2026Mono- 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.
- MakaleAçık Erişim2026In 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.
- MakaleYalnız künye2026Novel 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] .
- MakaleAçık Erişim2025Exploring 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.
- MakaleAçık Erişim2025Comprehensive 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.
- MakaleAçık Erişim2025Sulfonamide-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.
- MakaleAçık Erişim2024Determination of Antioxidant Capacities of Extracts of Sorbus subfusca (ledeb. ex. nordm.) boiss
Kocabaş, Selahattin; Topal, Fevzi
Sorbus subfusca (ledeb. ex. nordm.) boiss. (Sorbus subfusca) belongs to the Rosacese family. It is commonly referred to as highland rowan. It is an endemic species found only in the eastern Black Sea Region of Turkey and in a few countries on the Asian Continent. Both water (WESS) and ethyl alcohol (EESS) lyophilized forms were used as extracts. Different reducing capacity methods and radical scavenging activity methods were used to study the antioxidant activities of the extracts. Total phenolic compounds were calculated as 43.5 (WESS) and 43.0 (EESS) µg GAE/mg extract. This value is an indication that it can take place in plants with high phenolic content. Peroxidation inhibition percentages of linoleic acid emulsion at 20 µg mL-1 concentration for WESS and EESS; WESS was calculated as 70.93% and EESS as 82.63%. The high antioxidant capacity of Sorbus subfusca, an endemic species, brings up the preference of natural products as antioxidants. It is thought that these studies will draw a new path to the literature, especially alternative medicine and pharmacological studies.
- MakaleAçık Erişim2024Exploring 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.
- MakaleYayıncıda açık erişim2024Novel 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.
- MakaleAçık Erişim2024Design 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
- MakaleYalnız künye2023LC-HRMS Profiling and Phenolic Content, Cholinesterase, and Antioxidant Activities of Terminalia citrina
Özler, Ebubekir; Topal, Fevzi; Topal, Meryem; Öztürk Sarıkaya, Sevim Beyza
Terminalia citrina (T. citrina) belongs to the Combretaceae family and is included in the class of medicinal plants in tropical countries such as Bangladesh, Myanmar, and India. The antioxidant activities of lyophilized water (WTE) and alcohol extracts (ETE) of T. citrina fruits, their phenolic content by LC-HRMS, and their effects on cholinesterases (ChEs; AChE, acetylcholinesterase, and BChE, butyrylcholinesterase) were investigated. Especially ten different analytical methods were applied to determine the antioxidant capacity. Compared with similar studies for natural products in the literature, it was determined that both WTE and ETE exhibited strong antioxidant capacity. Syringe and ellagic acids were higher than other acids in ETE and WTE. IC50 values for ETE and WTE in DPPH radical and ABTS⋅+ scavenging activities were calculated as 1.69–1.68 μg mL−1 and 6.79–5.78 μg mL−1, respectively. The results of the biological investigations showed that ETE and WTE had an inhibition effect against ChEs, with IC50 values of 94.87 and 130.90 mg mL−1 for AChE and 262.55 and 279.70 mg mL−1 for BChE, respectively. These findings indicate that with the prominence of herbal treatments, T. citrina plant may guide the literature in treating Alzheimer's Disease, preventing oxidative damage, and mitochondrial dysfunction.
- MakaleYalnız künye2021Inhibition Profiles of Some Symmetric Sulfamides Derived from Phenethylamines on Human Carbonic Anhydrase I, and II Isoenzymes
Topal, Fevzi; Aksu, Kadir; Gulcin, Ilhami; Tümer, Ferhan; Goksu, Süleyman
In this work, the inhibitory effect of some symmetric sulfamides derived from phenethylamines were determined against human carbonic anhydrase (hCA) I, and II isoenzymes, and compared with standard compound acetazolamide. IC50 values were obtained from the Enzyme activity (%)-[Symmetric sulfamides] graphs. Also, Ki values were calculated from the Lineweaver-Burk graphs. Some symmetric sulfamides compounds (11–18) demonstrated excellent inhibition effects against hCA I, and II isoenzymes. These compounds demonstrated effective inhibitory profiles with IC50 values in ranging from 21.66–28.88 nM against hCA I, 14.44–30.13 nM against hCA II. Among these compounds, the best Ki value for hCA I (Ki: 8.34±1.60 nM) and hCA II (Ki: 16.40±1.00 nM) is compound number 11. Besides, the IC50 value of acetazolamide used as a standard was determined as hCA I, hCA II 57.75 nM, 49.50 nM, respectively. Moreover, in silico ADME-Tox study showed that all synthesized compounds (11–18) had good oral bioavailability in light of Jorgensen's rule of three, and of Lipinski's rule of five.
- MakaleYalnız künye2021Determination 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.
- MakaleAçık Erişim2021LC-HRMS Profiling and Antidiabetic, Anticholinergic, and Antioxidant Activities of Aerial Parts of Kinkor (Ferulago stellata)
Kiziltas, Hatice; Bingol, Zeynebe; Gören, Ahmet Ceyhan; Kose, Leyla Polat; Durmaz, Lokman; Topal, Fevzi; Alwasel, Saleh H.; Gulcin, Ilhami
Kinkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kinkor (Ferulago stellata), some putative antioxidant methods such as DPPHGreek ano teleia scavenging activity, ABTS(center dot+) scavenging activity, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and alpha-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kinkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kinkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kinkor (Ferulago stellata) demonstrated IC50 values of 1.772 mu g/mL against acetylcholinesterase (AChE), 33.56 +/- 2.96 mu g/mL against alpha-glycosidase, and 0.639 mu g/mL against alpha-amylase enzyme respectively.
- MakaleAçık Erişim2019Determination of Antioxidant Capacity of 2,6-Quinolinediol
Topal, Fevzi
The compounds of the quinolone group have been widely used in the alive metabolism,paint and pharmaceutical industry. Therefore, various quinoline derivatives are synthesized andsynthesis methods are developed. The synthesis of the quinoline compounds in the industrial field isformed in a separate area. 2,6-quinolinediol is derivative a quinoline. In this study, differentbioanalytical methods such as reducing capacity by Fe3+-Fe2+ transformation method, Fe3+-TPTZreducing capacity by FRAP method, Cu2+-Cu+reducing capacity by CUPRAC method, the ferric ions(Fe2+) chelating activity by using bipyridyl reagent, DPPH, ABTS, DMPD radical scavengingactivities, superoxide anion radicals (O2.-) scavenging activity have been used. Also, Trolox, αTocopherol, BHA and BHT have been used as reference antioxidants. The IC50 inhibition value of theABTS radical removal activity for this substance was calculated as 3.39 µg mL-1. Referenceantioxidants such as trolox, BHA, α-Tocopherol and BHT exhibited ABTS radical removal inhibitionsat 2.59, 4.44, 7.07 and 32.36 µg mL-1, respectively. Studies have shown that 2,6-quinolinediol is aneffective antioxidant.
- MakaleAçık Erişim2019Anticholinergic and antidiabetic effects of isoeugenol from clove (Eugenia caryophylata) oil
Topal, Fevzi
Isoeugenol (2-methoxy-4-(prop-1-en-1-yl)phenol), a component of from clove (Eugenia caryophylata) oil, is a starting material for both the biotechnological and synthetic production of vanillin and vanillic acid. In this article, the isoeugenol showed excellent inhibitory effects against some metabolic enzymes such as acetylcholinesterase (AChE) enzymes, α-glycosidase, and α-amylase. Isoeugenol has the IC50 values of 411.5 for α-amylase, 19.25 nM for α-glycosidase and 77.00 nM for AChE. Ki values of isoeugenol were found as 21 ± 9 nM and 16 ± 3 nM against α-glycosidase and AChE, respectively. On the other hand, tacrine as standard AChE inhibitor exhibited IC50 value of 20.38 nM. α-Glycosidase inhibitors, commonly referred to as starch blockers, are anti-diabetic drugs that help reduce edible blood glucose levels. AChE inhibitors are used for the treatment of some neurologic degenerational diseases, which involve Alzheimer’s disease. Also, there is a growing interest and the need to search for newer effective and safe AChE, α-amylase, and α-glycosidase inhibitors for the treatment of some metabolic disorder.
- MakaleYalnız künye2019Inhibition profiles of Voriconazole against acetylcholinesterase, α-glycosidase, and human carbonic anhydrase I and II isoenzymes
Topal, Fevzi
In this work, the inhibitory activity of Voriconazole was measured against some metabolic enzymes, including human carbonic anhydrase (hCA) I and II isoenzymes, acetylcholinesterase (AChE), and α-glycosidase; the results were compared with standard compounds including acetazolamide, tacrine, and acarbose. Half maximal inhibition concentration (IC50) values were obtained from the enzyme activity (%)-[Voriconazole] graphs, whereas Ki values were calculated from the Lineweaver-Burk graphs. According to the results, the IC50 value of Voriconazole was 40.77 nM for α-glycosidase, while the mean inhibition constant (Ki) value was 17.47 ± 1.51 nM for α-glycosidase. The results make an important contribution to drug design and have pharmacological applications. In addition, the Voriconazole compound demonstrated excellent inhibitory effects against AChE and hCA isoforms I and II. Voriconazole had Ki values of 29.13 ± 3.57 nM against hCA I, 15.92 ± 1.90 nM against hCA II, and 10.50 ± 2.46 nM against AChE.