Browsing by Author "Turgut, Gurbet Celik"

Now showing 1 - 5 of 5

Citation - WoS: 30
Citation - Scopus: 30
Synthesis of Nitrogen-Containing Oleanolic Acid Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors
(Springer Birkhauser, 2023) Senol, Halil; Turgut, Gurbet Celik; Sen, Alaattin; Saglamtas, Rueya; Tuncay, Salih; Gulcin, Ilhami; Topcu, Guelacti
In this study, a total of 13 compounds (5-17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds (10, 11, 12, 15 and 17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. Compounds 13 and 15 showed better inhibitory activity than the other compounds against both hCA I and hCA II isoenzymes, which are competing with AZA. In addition, compound 15 showed the strongest AChE inhibitory activity among all the tested compounds, with an IC50 value of 34.46 mu M.
Citation - WoS: 4
Citation - Scopus: 4
Natural Diterpenoid Alysine a Isolated from Teucrium Alyssifolium Exerts Antidiabetic Effect via Enhanced Glucose Uptake and Suppressed Glucose Absorption
(Tubitak Scientific & Technological Research Council Turkey, 2019) Sen, Alaattin; Ayar, Buket; Yilmaz, Anil; Acar, Ozden Ozgun; Turgut, Gurbet Celik; Topcu, Gulacti
Teucrium species have been used in folk medicine as antidiabetic, antiinflammatory, antiulcer, and antibacterial agents. We have explored in vitro antidiabetic impacts of 2 natural diterpenoids, alysine A and alysine B, isolated from Teucrium alyssifolium. The lactate dehydrogenase (LDH) cytotoxicity assay, glucose uptake test, glucose utilization (glycogen content) test, glucose transport test, glucose absorption (a-glucosidase activity) test, insulin secretion test, RNA isolation and cDNA synthesis assay, qPCR quantification assays, and statistical analyses were carried out in the present study. Alysine A exerted the following effects at non-cytotoxic doses: Enhanced the glucose uptake, as much as the insulin in the C2C12, HepG2, and 3T3-L1 cells Increased the glycogen content in the C2C12 and HepG2 liver cells, significantly higher than the insulin and metformin Suppressed the alpha-glucosidase and the GLUT2 expression levels in the Caco-2 cells Suppressed the SGLT1 and GLUT1-5 expression levels in the Caco-2 cells Induced the insulin receptor substrate (IRS)1 and GLUT2 expression levels of the BTC6 pancreatic cells Induced the insulin receptor (INSR), IRS2, phosphoinositide 3-kinase (PI3K), GLUT4, and protein kinase (PK) expression levels of the 3T3-L1 and C2C12 cells Increased glucose transport through the Caco-2 cell layer Did not influence insulin secretion in the pancreatic BTC6 cells Consequently, these data strongly emphasized the antidiabetic action of alysine A on the particularly critical model mechanisms that assume a part in glucose homeostasis, such as glucose uptake, utilization, and storage. Moreover, the expression level of the essential genes in glucose metabolism and insulin signaling was altered in a way that the results would be antihyperglycemic. A blend of in vitro and in situ tests affirmed the antihyperglycemic action of alysine A and its mechanism. Alysine A has exercised significant and positive results on the glucose homeostasis; thus, it is a natural and pleiotropic antidiabetic agent. Advanced in vivo studies are required to clarify the impact of this compound on glucose homeostasis completely.
Citation - WoS: 4
Citation - Scopus: 6
Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches
(Wiley-VCH Verlag GmbH, 2022) Orhan, Ilkay Erdogan; Deniz, F. Sezer Senol; Salmas, Ramin Ekhteiari; Irmak, Sule; Acar, Ozden Ozgun; Turgut, Gurbet Celik; Tataringa, Gabriela
Series of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23 +/- 2.91 mu M, while the reference (galantamine) had IC50=1.85 +/- 0.12 mu M. Compounds 9 (IC(50)75.14 +/- 1.82 mu M), 13 (IC50=16.14 +/- 0.43 mu M), were determined to be stronger BChE inhibitors than the reference galantamine (IC50=93.53 +/- 2.23 mu M). The IC50 value of compound 16 for BChE inhibition (IC50=126.56 +/- 11.96 mu M) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.
Citation - WoS: 5
Citation - Scopus: 5
Therapeutic Potential of Nitrogen-Substituted Oleanolic Acid Derivatives in Neuroinflammatory and Cytokine Pathways: Insights From Cell-Based and Computational Models
(Wiley-VCH Verlag GmbH, 2025) Turgut, Gurbet Celik; Pepe, Nihan Aktas; Ekiz, Yagmur Ceylan; Senol, Halil; Sen, Alaattin
This study was conducted to investigate the mechanism of the potential and anti-inflammatory properties of nitrogen-substituted oleanolic acid derivatives that can be used to treat neuroinflammatory diseases. Nitrogen-containing oleanolic acid derivatives have been evaluated for their anti-neuroinflammatory effects in vitro in neuronal and monocytic cell lines at nontoxic doses, and the production of cytokines (TNF-alpha, IL-6 and IL-17), the inflammatory enzyme induced nitric oxide synthase (iNOS) and NF-kappa B signalling under LPS-stimulated conditions, and the expression of genes associated with Alzheimer's disease have been assessed. In addition, molecular docking and molecular dynamics simulation assessments are conducted in silico. Key protein markers of neurodegenerative diseases, especially Alzheimer's disease and neuroinflammation, TAU protein levels, and microglial activation, as well as ionised calcium-binding adaptor protein-1 (IBA1) levels, were significantly reduced with the addition of oleanolic acid derivatives. LPS-induced NF-kappa B luciferase reporter activity and iNOS activity were significantly inhibited, approaching the levels in uninduced controls. The mRNA expression of proinflammatory cytokines critical for neuroinflammation, such as TNF-alpha, NF-kappa B, IL-6 and IL-17, was reduced twofold to sevenfold. Furthermore, the molecular docking and MD simulation analyses revealed potential interactions with the TNF-alpha and NF-kappa B proteins. These findings underscore the potential of oleanolic acid derivatives, particularly compound 16, as candidates for further development as therapeutic agents for neurodegenerative diseases associated with chronic inflammation.
Synthesis, Characterization, and Comprehensive in Vitro and in Silico Evaluation of the Anti-Inflammatory Potential of Novel 1,2,3-Triazole–Arylidenehydrazide/Thiazolidinone Hybrids
(Wiley-VCH verlag GmbH, 2025) Pepe, Nihan Aktas; Cakir, Furkan; Atalay, Tugba; Acar, Busra; Turgut, Gurbet Celik; Sen, Alaattin; Senol, Halil
Five novel 1,2,3-triazole/arylidenehydrazide/thiazolidinone hybrid compounds (7-11) were synthesized and characterized using NMR, HRMS, IR, and HPLC purity analysis. The cytotoxicity of these compounds was evaluated on fibroblasts and THP-1 cells, showing that all compounds were nontoxic at the tested concentrations. The wound healing assay revealed that compounds 7, 9, and 10 significantly enhanced wound closure, with a 7.74%-32.69% improvement in treated cells. Compounds 8 and 11 showed moderate effects. Anti-inflammatory activity was assessed through qRT-PCR, demonstrating that compound 10 led to the most significant reduction in proinflammatory cytokines TNF-alpha, IL-1 beta, and NF-kappa B1. In addition, the expression of Iba1 protein in THP-1 cells confirmed that compound 8 showed the strongest anti-inflammatory effect, surpassing that of aspirin. Compound 10 showed the highest inhibition of NF-kappa B signaling and iNOS activity. Molecular docking studies revealed that compounds 10 and 11 had strong binding affinities to TNF-alpha and iNOS, with compound 11 showing the most stable interactions. Molecular dynamics simulations supported these findings, indicating that compound 11 demonstrated more stable binding to both targets. Overall, the results suggest that compounds 10 and 11 are promising anti-inflammatory candidates with potential for further development in therapeutic applications for inflammatory diseases.