Sürdürülebilir Kalkınma Amaçları
Yazarlar
- Ekincioğlu, Yavuz(3)
- Aslan, Osman Nuri(2)
- Can, Zehra(2)
- Demir, Yeliz(2)
- Kalay, Erbay(2)
- Kara, Yakup(2)
- Kolayli, Sevgi(2)
- Kızıl, Hamit Emre(2)
- Nartop, Dilek(2)
- Şahin, Engin(2)
- Adem, Şevki(1)
- Ay Şal, Fulya(1)
- Ağar, Güleray(1)
- Beldüz, Ali Osman(1)
- Dereli, Ömer(1)
- Ekincioglu, Yavuz(1)
- Eyupoglu, Volkan(1)
- Guler, Halil Ibrahim(1)
- Güler, Halil İbrahim(1)
- Güllü, Eda(1)
- Gündoğdu, Özlem(1)
- Karakaş Sarıkaya, Ebru(1)
- Kilinç, Namık(1)
- Kishali, Nurhan(1)
- Kizil, Hamit Emre(1)
- Kostak, Feyza(1)
- Ozkok, Asli(1)
- Pehlivanoğlu, Suray(1)
- Pezik, Esra(1)
- Rawat, Ravi(1)
- Sahin, Huseyin(1)
- Serdar, Umit(1)
- Tanrıverdi, Aslıhan Aycan(1)
- Tanrıverdi, Erdi Anıl(1)
- Türkeş, Cüneyt(1)
- Türkmen, Merve Özcan(1)
- Ulcay, Sibel(1)
- Yetim, Nurdan Kurnaz(1)
- Yildiz, Oktay(1)
- Yıldıko, Ümit(1)
Yayınlar
- MakaleAçık Erişim2026Scopus SJRQ2Rhodanine–Sulfonate hybrids targeting aldose reductase: Synthesis, in vitro inhibition, molecular docking, and cytotoxicity studies
Kalay, Erbay; Demir, Yeliz; Türkeş, Cüneyt; Aslan, Osman Nuri; Pezik, Esra; Şahin, Engin
Aldose reductase (ALR2), a key enzyme in the polyol pathway, plays a significant role in the onset and progression of diabetic complications, rendering it a critical pharmacological target. In this study, a novel series of twenty-four sulfonate ester-functionalized rhodanine derivatives (compounds 1–24) were rationally designed, synthesized via Knoevenagel condensation, and comprehensively evaluated for their inhibitory activity against ALR2. Spectroscopic and spectrometric methods confirmed the structural integrity of the synthesized compounds. In vitro enzyme inhibition assays revealed that all compounds acted as competitive inhibitors, with several analogues, particularly compounds 6 and 8, exhibiting stronger ALR2 inhibition (Ki = 0.43 µM and 0.48 µM, respectively) than the reference drug epalrestat (Ki = 0.98 µM). Structure–activity relationship (SAR) analysis highlighted the critical influence of para-substituted electron-donating (e.g., methyl) and electron-withdrawing (e.g., nitro, halogen) groups on binding potency. Molecular docking of the most potent inhibitor (compound 6) demonstrated a stable binding pose supported by key interactions, including hydrogen bonding with His110 and π–π stacking with Phe122. In silico ADME profiling confirmed favorable drug-likeness properties for all derivatives. Cytotoxicity studies on L929, A549, and RG-2 cell lines revealed that most compounds were less toxic than the reference drug at lower concentrations, with compound 8 showing a promising cytotoxic profile. These findings position rhodanine–sulfonate hybrids as promising scaffolds for the development of next-generation ALR2 inhibitors for the treatment of diabetic complications.
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İncele - MakaleAçık Erişim2026Scopus SJRQ2Synthesis and pharmacokinetic profiling of a novel pyrimidine imidazole based thiosemicarbazone derivative for BRAF inhibition in lung cancer therapy
Ekincioğlu, Yavuz; Kızıl, Hamit Emre; Güllü, Eda; Özkan, Elvan Hasanoğlu; Nartop, Dilek
This study presents the design, synthesis, and comprehensive evaluation of a novel thiosemicarbazone derivative containing a pyrimidine-imidazole (C11H11N8SCl) as a potential BRAF inhibitor for the treatment of non-small cell lung cancer. The compound was synthesized by a condensation reaction and characterized by elemental analysis, molar conductivity, SEM-EDS, FT-IR, 1H, and 13C-NMR spectral techniques. DFT calculations at the B3LYP/6-311 + + G(d, p) level revealed a HOMO-LUMO gap of 2.8 eV, indicating appropriate molecular stability and reactivity. Molecular docking studies with BRAF (PDB ID: 1UWH) demonstrated favorable binding affinity (-6.85 kcal/mol) with key interactions at ILE512, HIS509, HIS584, GLN529, GLU585, LYS590, VAL510, and LEU587 residues. In vitro cytotoxicity assays revealed that the compound possesses anticancer potential against H-460 cells, with a significant inhibitory effect observed at a concentration of 200 µg/mL. Combined with its favorable binding affinity toward BRAF kinase, these results suggest that the pyrimidine-imidazole thiosemicarbazone may serve as a potential lead scaffold for further development in targeted lung cancer therapy.ADME profiling confirmed the compound’s compliance with Lipinski’s rule of five parameters, supporting its potential as an orally active drug candidate. These findings suggest that our pyrimidine-imidazole thiosemicarbazone represents a promising scaffold for the development of targeted BRAF inhibitors for lung cancer therapy.
- MakaleYalnız künye2026Scopus SJRQ2Novel heteroaromatic compounds bearing thiosemicarbazone as anti-cancer and anti-bacterial agents: Synthesis, cytotoxic and biological screening, molecular docking and DFT analysis
Nartop, Dilek; Ögütcü, Hatice; Özkan, Elvan Hasanoglu; Yetim, Nurdan Kurnaz; Kizil, Hamit Emre; Ekincioglu, Yavuz
Novel heteroaromatic compounds (Hc1, Hc2, Hc3, Hc4) were obtained, and their structure were confirmed using various spectroscopic methods, including elemental analysis, fourier transform infrared (FT-IR) spectroscopy, proton and carbon nuclear magnetic resonance (1H/13C-NMR) spectroscopy, and molar conductance measurement. The biological activities of the heteroaromatic compounds against several Gram-positive (Micrococcus luteus ATCC9341, Staphylococcus epidermidis ATCC12228, Bacillus cereus RSKK863, Listeria monocytogenes ATCC 19111), and Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC27853, Klebsiella pneumonia ATCC27853, Enterobacter aerogenes ATCC51342, Salmonella typhi H NCTC9018394, Shigella dysenteriae NCTC2966, Proteus vulgaris RSKK96026) were evaluated using the well-diffusion method. In general, the heteroaromatic compounds demonstrated a stronger inhibitory effect against Gram-positive bacteria. Hc1, Hc2 and Hc3 showed the highest inhibitory effect against B. cereus and L. monocytogenes. The compound (Hc4) showed the highest antibacterial activity and antifungal activity against Bacillus cereus and C. albicans, respectively. The cytotoxic activity of the heteroaromatic compounds was assessed against the non-small cell lung cancer cell line (NCI-H460) using the NutriCulture Cell Viability Detection Kit-8 (CVDK-8). Among the synthesized heteroaromatic compounds, Hc3 exhibited significant cytotoxic activity with an IC50 value of 141.3 & micro;g/mL, whereas compounds Hc1, Hc2, and Hc4 did not display significant toxicity at the tested concentrations. The molecular geometry of the heteroaromatic compound (Hc3) was optimized using Gaussian 09 W at the B3LYP/6-311++G (d,p) level of theory. Key structural parameters such as bond lengths, bond angles, and dihedral angles were determined through the same computational framework. Electronic features, including frontier molecular orbitals, global reactivity descriptors, and molecular electrostatic potential surfaces, were analyzed to explore intramolecular charge distribution and predict reactive sites. To evaluate the biological potential of the heteroaromatic compound (Hc3), molecular docking studies were performed. Additionally, drug-likeness assessment based on Lipinski's Rule of Five and ADME profiling revealed favorable pharmacokinetic characteristics. Molecular docking studies revealed that compound Hc3 showed a binding energy of -4.09 kcal/mol against the EGFR target (PDB ID: 1UWH), exhibiting key interactions such as hydrogen bonding and It-interactions with the active site residues. Based on all the results, it can be said that new heteroaromatic compounds have significant potential in the pharmaceutical field.
AtıfScopus1OpenAlex1İncele - MakaleAçık Erişim2025Scopus SJRQ4DFT Calculations, ADME Analysis and Molecular Docking Studies of the Compound AHTPO With the Digestive Enzyme Trypsin Found in Cold-Adapted Fish Species
Tanrıverdi, Erdi Anıl; Tanrıverdi, Aslıhan Aycan; Yıldıko, Ümit
For the special amine 7-Amino-3-(4-aminophenyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (AHTPO), previously reported experimental biological activities served as the foundation for further studies. Computational chemistry and molecular simulation techniques were subsequently applied to investigate AHTPO. Its interactions with trypsin enzymes derived from cold-adapted fish species were examined. The compound's biological activity and pharmacokinetic properties were assessed using DFT calculations, molecular docking, and ADME analyses. Molecular docking results indicated that AHTPO exhibits strong binding affinities with the 1A0J and 2TBS enzymes, with the binding to 2TBS being energetically more favorable. Additionally, ADME analysis revealed that while the AHTPO shows potential for pharmaceutical applications, its gastrointestinal absorption and blood-brain barrier permeability may present certain limitations. Regarding its electronic and optical properties, AHTPO's high dipole moment and polarizability values enhance its flexibility and adaptability in biological environments. The HOMO-LUMO energy gap suggests that the AHTPO achieves a balance between stability and reactivity, enabling high activity in biomolecular interactions. These findings highlight the promising pharmacological potential of AHTPO in binding with trypsin enzymes, suggesting its viability as a therapeutic agent.
AtıfScopus1OpenAlex1İncele - MakaleAçık Erişim2025Scopus SJRQ2An Integrated In Vitro and In Silico Investigation of the Bioactive Properties of Wild Glycyrrhiza glabra var. glandulifera
Kızıl, Hamit Emre; Ulcay, Sibel; Ekincioğlu, Yavuz; Öğütçü, Hatice; Ağar, Güleray
This investigation examined methanol extracts obtained from the whole plant (encompassing all organs except roots), flowers, and fruits of wild Glycyrrhiza glabra var. glandulifera, a liquorice cultivar indigenous to the Cappadocia region of Türkiye, constituting the first comprehensive in vitro and in silico analysis of this species within the region. Anatomical identification revealed distinctive structural characteristics, including thick-walled epidermal cells in the stem, organized clusters of collenchyma cells, and well-defined sclerenchyma layers encompassing the vascular bundles. The petiole exhibited a characteristic heart-shaped morphology containing three vascular bundles, while foliar analysis demonstrated the presence of stomata on both adaxial and abaxial surfaces, accompanied by a bifacial mesophyll arrangement. The extracts demonstrated remarkable antimicrobial efficacy against both Gram-positive and Gram-negative bacteria, as well as various fungal species. Furthermore, significant cytotoxic activity was observed against non-small cell lung cancer (H460), with the whole plant extract exhibiting IC50 values of 117.8 µg/mL (24 h) and 105.6 µg/mL (48 h). Flower extracts demonstrated IC50 values of 116.8 µg/mL (24 h) and 112.7 µg/mL (48 h), while fruit extracts displayed superior potency with IC50 values of 104.4 µg/mL (24 h) and 63.09 µg/mL (48 h). Molecular docking analyses, conducted utilizing AutoDock Tools 1.5.6 and BIOVIA Discovery Studio Visualizer 4.5, revealed significant protein-ligand interactions, yielding optimal binding energy and inhibition constant values of -9.57 kcal/mol and 96.92 nM, respectively. The RMSD values were calculated based on structural variations between ligand-protein complexes during re-docking procedures. These findings underscore the substantial biological potential of Glycyrrhiza glabra var. glandulifera from Cappadocia, necessitating further comprehensive investigation.
AtıfScopus6WoS6OpenAlex5İncele - MakaleAçık Erişim2025Scopus SJRQ1Anticancer (cytotoxic, anticlonogenic, antimetastatic, immunomodulatory actions) properties of 3,5-dibromosalicylaldehyde against glioblastoma cells and DFT analyses (FT-IR, Raman, NMR, UV) as well as a molecular docking study
Karakaş Sarıkaya, Ebru; Pehlivanoğlu, Suray; Türkmen, Merve Özcan; Ekincioğlu, Yavuz; Kostak, Feyza; Çelik, Sultan; Dereli, Ömer
Background Information: The primary objectives of this study were to characterize 3,5-dibromosalicylaldehyde (3,5-DBSA) and, investigate its antiproliferative, antimetastatic, cytotoxic, and immunoregulatory properties. NMR, Raman, UV, and FT-IR spectroscopies were used to characterize 3,5-DBSA. Potential conformations of 3,5-DBSA were evaluated using Spartan's MMFF method. Geometry optimization calculations using Gaussian software calculated conformation energy values. Results: Subsequently, Raman, FT-IR, UV (ethanol) and NMR (DMSO) parameters were calculated. The experimental spectrum was compared to theoretical spectroscopic data. The present investigation investigated 3,5-DBSA's anticancer properties; therefore, docking was done once the stable structure had been identified. Conclusion: Identifying stable structure is crucial to molecular docking studies. In order to identify the mechanism by which 3,5-DBSA binds to PI3K as a therapeutic target, molecular docking was utilized. This work is the first to show that 3,5-DBSA is cytotoxic, anticlonogenic, antimetastatic, and immunomodulatory in glioblastoma cell line U87MG compared to healthy fibroblast L929 cells. Cytotoxicity and anti-clonogenicity studies investigated 3,5-DBSA's antiproliferative activities, whereas wound healing assays assessed cell migration. The immunomodulatory effects of 3,5-DBSA in glioblastoma were assessed by measuring Netrin-1 and IL-6 protein levels. According to our findings, 3,5-DBSA may treat glioblastoma. Significance: This work analyzes 3,5-DBSA's conformational search, characterization, molecular docking, and structural and anticancer properties.
- MakaleAçık Erişim2025Scopus SJRQ1Design, synthesis, and inhibition of α-glucosidase by novel L-phenylalanine-derived hydrazones: Kinetic, molecular docking, and dynamics studies
Kalay, Erbay; Adem, Şevki; Demir, Yeliz; Aslan, Osman Nuri; Şahin, Engin; Eyupoglu, Volkan; Rawat, Ravi; Çomaklı, Veysel
In this paper, a series of novel hydrazones derived from L-phenyl alanine were synthesized in four steps and employed to inhibit α-glucosidase through kinetic studies, molecular docking, and molecular dynamics analyses. Among the synthesized compounds, 8, 15, and 16 exhibited the strongest inhibitory effects, with IC50 values of 31.08 μM, 24.15 μM, and 19.47 μM, respectively, surpassing the standard inhibitor acarbose (79.63 μM). Molecular docking studies revealed robust interactions, with compound 16 achieving the highest MolDock score of −176.316. Molecular dynamics simulations were conducted to evaluate the binding affinity of compound 16 to the isomaltase enzyme from Saccharomyces cerevisiae (3A4A). The most favorable docking pose was subjected to further analysis through MD simulations under dynamic conditions. The MMGBSA analysis of the simulation cluster indicated a strong binding affinity of approximately −43.06 kcal/mol, highlighting the compound's potential for modulating α-glucosidase activity. These results underscore the potential of bromine and hydroxyl-substituted hydrazones to modulate isomaltase activity, with therapeutic implications for hyperglycemia and obesity management.
AtıfScopus12WoS12OpenAlex16İncele - MakaleAçık Erişim2024Scopus SJRQ3A Study on Recognizing the Value of Chestnut (Castanea sativa) Blossom Waste
Sahin, Huseyin; Kolayli, Sevgi; Kara, Yakup; Can, Zehra; Guler, Halil Ibrahim; Ozkok, Asli; Serdar, Umit
Chestnut (Castanea sativa) blossoms are natural resources that are not put to economic use. They are completely mixed with soil as waste. Thus, this extensive study was designed and remarkable results were found showing the potential usefulness of chestnut blossoms. In addition to the phenolic capacity and antioxidant capacity of the aqueous and ethanolic extracts of dried chestnut flowers, the anti-urease activity of these extracts was studied to demonstrate their therapeutic value. The binding interaction of phenolic substances present in chestnut blossom with urease was shown using molecular docking research. The aqueous extract, with most effect, had total phenolic content of 46.67 ± 0.37 mg GAE/g and total flavonoid content of 6.14 ± 0.40 mg QUE/g. The antioxidant activity was determined by FRAP (648.47 ± 5.27 µmol FeSO4.7H2O/g for aqueous extract and 347.53 ± 2.09 µmol FeSO4.7H2O/g for ethanolic extract) and DPPH (0.05 ± 0.01 mg/mL for SC50 of aqueous extract and 0.11 ± 0.01 mg/mL for SC50 of ethanolic extract) assays, and rutin was found to be the dominant phenolic compound according to HPLC. IC50 values for urease in aqueous and ethanolic extracts were 2.55 ± 0.09 mg/mL and 4.57 ± 0.24 mg/mL, respectively. According to the docking experiments, which were important to support the hypothesis of anti-urease activity, myricetin and luteolin showed different and effective bonding degrees to the target protein when compared with the reference molecule acetohydroxamic acid. In summary, chestnut flowers are rich in phenolic compounds which are responsible for a wide range of biological activities including antioxidant features and urease inhibition. These blossoms could be evaluated as potentially important raw materials for food.
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İncele - MakaleYalnız künye2024Scopus SJRQ3Exploring the Potential of Isoindole-1,3-Dione Derivatives as Novel Inhibitors of Aldose Reductase: An In Silico and In Vitro Insight into Therapeutic Strategies for Diabetic Complications
Şengül, Bülent; Gündoğdu, Özlem; Kilinç, Namık; Kishali, Nurhan
This study explores the potential of isoindole-1,3-dione derivatives as novel inhibitors of aldose reductase (AR), focusing on their in silico and in vitro effects for therapeutic strategies against diabetic complications. Aldose reductase, a critical enzyme in the polyol pathway, plays a significant role in glucose metabolism and has been linked to diabetic complications. In this comprehensive study, isoindole-1,3-dione derivatives were synthesized and evaluated for their inhibitory effects on the recombinant human AR enzyme. The compounds’ inhibitory activities were measured both in vitro and through in silico techniques, employing molecular docking and free binding energy calculations and ADME studies. The newly synthesized compounds demonstrated varied inhibitory effects, with ethyl and phenyl substituents at specific positions enhancing inhibitory activity. Notably, compounds with carboxylic acid derivatives exhibited potent inhibitory effects, especially compound 6 with an IC50 value of 1.649 μM. In conclusion, this study provides valuable insights into the inhibitory potential of isoindole-1,3-dione derivatives against AR, suggesting their potential therapeutic application in mitigating diabetic complications. The combination of experimental and computational approaches offers a comprehensive understanding of the compounds’ interaction mechanisms and pharmacokinetic profiles, supporting their further exploration as antidiabetic agents.
- MakaleAçık Erişim2021Scopus SJRQ2Targeting cov-2 spike rbd and ace-2 interaction with flavonoids of anatolian propolis by in silico and in vitro studies in terms of possible covid-19 therapeutics
Güler, Halil İbrahim; Ay Şal, Fulya; Can, Zehra; Kara, Yakup; Yildiz, Oktay; Beldüz, Ali Osman; Çanakçi, Sabriye; Kolayli, Sevgi
Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 protein were calculated separately with a molecular docking study using the AutoDock 4.2.6 program. In addition, the pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. The binding energy value of pinocembrin was highest in both receptors, followed by chrysin, CAPE, and hesperetin. Based on the in silico modeling and ADME (absorption, distribution, metabolism, and excretion) behaviors of the eight polyphenols, the compounds exhibited the potential ability to act effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against the Covid-19 virus. However, further studies are now needed.
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