WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article In Vitro Investigation of the Effects of Octenidine Dihydrochloride on Nasal Septum Squamous Carcinoma Cells(MDPI, 2025) Ciftci, Ihsan Hakki; Ozkan, Asuman Deveci; Erman, Gulay; Kilbas, Elmas Pinar Kahraman; Koroglu, Mehmet; Kahraman Kilbas, Elmas Pinar; Deveci Ozkan, AsumanBackground/Objectives: The aim of this study was to investigate the cytotoxic, genotoxic, apoptotic, and anti-inflammatory effects of the antiseptic agent octenidine dihydrochloride (OCT-D) on the RPMI-2650 cell line derived from human nasal mucosa in vitro. Methods: RPMI-2650 cells and Human Umbilical Cord Endothelial Cells (HUVECs) were treated with various concentrations of OCT-D (0.00625-0.4%) for 12 and 24 h. Cell viability was assessed using the WST-1 assay, while DNA damage was assessed using the comet and micronucleus (MN) assays. Apoptotic activity was determined using Annexin V flow cytometry and fluorescence microscopy. Intracellular reactive oxygen species (ROS) levels were measured, and inflammatory cytokines (IL-1 beta, IL-6, TNF-alpha, and IFN-gamma) were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of genes associated with apoptosis, oxidative stress, and inflammation was analyzed using RT-PCR. Results: OCT-D caused dose- and time-dependent cytotoxicity, and RPMI-2650 cells showed greater resistance compared to HUVECs. While a strong apoptotic response was observed in HUVECs, RPMI-2650 cells exhibited limited apoptosis. OCT-D was found to cause dose-dependent DNA damage and an increase in MN in both cell lines. OCT-D significantly reduced cytokine levels and ROS production in both cell types. RT-PCR results supported its anti-inflammatory and antioxidant effects at the molecular level. Conclusions: In conclusion, this study demonstrated that OCT-D exhibited minimal cytotoxic and apoptotic effects in RPMI-2650 cells, but affected vascular structure by inducing apoptosis in endothelial cells. These findings provide important evidence that OCT-D can be used as a potential adjunctive agent in nasal treatments, and these data need to be supported by preclinical and clinical studies.Article Synthesis, Molecular Modeling, Anti-Cancer and COX-1/2 Inhibitory Activities of Novel Thiazolidinones Containing Benzothiazole Core(Bangladesh Pharmacological Society, 2024) Kulabas, Necla; Guven, Cansu Tamniku; Duracık, Merve; Bingol Ozakpinar, Ozlem; Küçükgüzel, İlkay; Ozakpinar, Ozlem BingolIn this study, new 1,3-thiazolidin-4-one derivatives containing arylmethylene groups in the 5-position were obtained from 6-(trifluoromethoxy)-1,3-benzo-thiazol-2-amine (riluzole). Synthesized compounds were characterized by spectral data and elemental analysis. In vitro, cytotoxic activities of the synthesized molecules were evaluated against the human lung cancer (A549) and human prostate cancer (PC-3) cell lines. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Ten target compounds 3-12 were also screened for their COX-1 and COX-2 inhibitory activities. Of these compounds, 4 showed the highest COX-2 inhibition at 10 μM. Molecular docking calculations were performed to understand the binding interactions of compounds with COX-1 and COX-2 proteins. In silico studies of the tested compounds represented important binding modes that may be responsible for their anti-cancer activity via selective inhibition of the COX-2 enzyme. ADMET predictions were conducted to assess the drug-like properties of the novel compounds. © 2024 Elsevier B.V., All rights reserved.Article Design and Synthesis of Thiosemicarbazides and 1,2,4-Triazoles Derived From Ibuprofen as Potential Metap (Type II) Inhibitors(Elsevier Ireland Ltd, 2025) Yilmaz, Ozgur; Biliz, Yagmur; Ayan, Sumeyra; Cevik, Ozge; Karahasanoglu, Mufide; Cotuker, Reyhan; Kucukguzel, S. GunizIn the present study, a range of novel thiosemicarbazides 4a-i and 1,2,4-triazoles 5a-i derived from ibuprofen, were synthesized. Structural elucidation of these synthesized compounds was performed utilizing a variety of spectroscopic methods, including FTIR, 1H NMR, 13C NMR and HR-MS. The synthesized compounds were tested for cytotoxicity in five different cancer cell lines (cervical cancer (HeLa), human breast cancer (MCF-7), human gastric adenocarcinoma (MKN-45), human metastatic prostate cancer (PC3) and human glioblastoma (U87)). The compounds were compared with healthy cells (NIH-3T3) and the most effective compounds were determined by means of the selectivity index. Thiosemicarbazides derived form ibuprofen 4i and 4d showed anticancer activity, while 1,2,4-triazoles derived form ibuprofen 5b, 5c, 5d, 5e, 5h, 5g showed anticancer activity in HeLa, MCF-7, MKN-45, PC3 and U87 cells. To test the stability of the protein-drug complexes all 18 compounds 4a-i and 5a-i were docked into the active site of the MetAP2 enzyme In general, computational inhibition constants values were correlated with the experimental values. The dynamic behavior of MetAP2-inhibitor complexes was analyzed using all atoms Molecular Dynamic (MD) simulations for 200 ns duration. MD revealed that the drugs bind in the active center of MetAP2 with stable RMSD and RMSF. In conclusion, in-silico results and in-vitro studies suggests that thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen may be novel anticancer drug candidates for treating cervical, breast, prostate, gastric and glioblastoma. Compounds provided induction of apoptotic proteins in the cell by inhibiting MetAP2 enzyme. Furthermore, the potential antioxidant activities of the compounds were evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. Among the compounds tested, 4a, 4b, 4e, 4f, 4h, and 4i exhibited values closely resembling the DPPH activity of the standards.Article Citation - WoS: 3Citation - Scopus: 3A Novel Petox-Based Nanogel Targeting Prostate Cancer Cells for Drug Delivery(Wiley-v C H verlag Gmbh, 2024) Gulyuz, Sevgi; Sessevmez, Melike; Ukuser, Gokcen; Khalily, Melek Parlak; Tiryaki, Selen; Sipahioglu, Tarik; Yilmaz, OzgurThis study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx nanogel) is created using hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) through a combination of living/cationic ring-opening polymerization (CROP) and alkyne-azide cycloaddition (CuAAC) "click" chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through 1H-NMR, and FT-IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose-dependent cytotoxicity. Drug-loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug-free nanogels. Targeting efficiency is examined using both peptide-conjugated and peptide-free nanogels, with the intracellular uptake of peptide 563-conjugated nanogels by tumor cells being 60-fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non-toxicity, and enhanced intracellular uptake in the tumor region. This study emphisizes an innovative PEtOx-based nanogel tailored for targeted drug delivery in prostate cancer. Developed using click chemistry, a valuable technique for chemical synthesis, it exhibits consistent nanogel formation with customizable sizes. In vitro, drug-loaded nanogel exhibits potent cytotoxicity against cancer cells. Notably, peptide-conjugated nanogels significantly boost tumor cell uptake, showcasing promising promising potential for effective cancer drug delivey.imageArticle Citation - WoS: 4Citation - Scopus: 4Determination of Chemical Composition and Antioxidant, Cytotoxic, Antimicrobial, and Enzyme Inhibition Activities of <i>rumex Acetosella</I> L. Plant Extract(Springer int Publ Ag, 2024) Kandemir, Sevgi Irtegun; Aktepe, Necmettin; Baran, Ayse; Baran, Mehmet Firat; Atalar, Mehmet Nuri; Keskin, Cumali; Khalilov, Rovshan; Irtegün Kandemir, SevgiPurpose The phenolic composition, antioxidant, antimicrobial activity, enzyme inhibition activity, and cytotoxic activity potentials of the plant Rumex acetosella L. (R. acetosella) were examined in this study. Materials and Methods: The chemical composition of R. acetosella methanol extract was identified by the LC-MS/MS method. The antioxidant activity was tested using beta-carotene/linoleic acid, DPPH free radical scavenging, ABTS cation radical scavenging, CUPRAC reducing power, and metal chelating activity methods. The cytotoxic activity was determined by the MTT assay using human ovarian adenocarcinoma (Skov-3), glioblastoma (U87), human dermal fibroblasts (HDF), and human colorectal adenocarcinoma (CaCo-2) cell lines. The antimicrobial activity of methanolic extracts was tested on gram-negative (Escherichia coli and Pseudomonas aeuriginosa) and gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) using the in vitro minimum inhibition concentration method (MIC). Enzyme inhibition activity of R. acetosella methanol extract was measured spectrophotometrically against acetylcholinesterase (AChE) and glutathione S-transferase (GST) enzymes. Results: The findings showed that the major components of the methanol extract content were luteolin-7-O-glucoside (1.599 m/L), polydatin (91,024 m/L), and shikimic acid (0.773 m/L). It was determined that the extract and standard antioxidant (a-tocopherol) results in DPPH center dot, and ABTS center dot + tests performed to determine the antioxidant activity were close to each other, and this value was more effective than the standard antioxidant (alpha-tocopherol) in the CUPRAC test. These results suggested that the plant's antioxidant potential was higher when compared with reference antioxidant compounds. It was determined that the methanol extract of R. acetosella had a weaker effect on the growth of the tested microorganisms than the antibiotics used as standard. The activity of the GST and AChE enzymes was found to be severely inhibited by the methanol extract of R. acetosella. Conclusion: Based on these findings, R. acetosella L. is a medicinal and commercially beneficial plant that warrants further investigation.Article Citation - WoS: 11Citation - Scopus: 11Synthesis and Biological Evaluation of Novel Aryloxyacetic Acid Hydrazide Derivatives as Anticancer Agents(Taylor & Francis inc, 2021) Senkardes, Sevil; Erdogan, Omer; Cevik, Ozge; Kucukguzel, S. GunizIn our continuing search for new anticancer agents, herein we report the synthesis of 2-(4-chloro-3-methylphenoxy)-N'-[(aryl)methylidene]acetohydrazides 3a-j and the evaluation of their anticancer activities on cell viability, morphological changes and caspase-3 activity in cancer cell lines including gastric cancer (MKN45), cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells. 2-(4-chloro-3-methylphenoxy)-N'-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g presented the strongest growth inhibition against MKN45 gastric cancer cell lines with the IC50 value of 1.471 +/- 0.23 mu M. Moreover, compounds 3b and 3g showed high potency against the HeLa and MDA-MB-231 cell lines having IC50 in the range of 2.38-9.72 mu M. These compounds are more selective for the tested human cancer cells than for the mouse fibroblast cell line (NIH/3T3). As a result of the studies conducted in order to understand the molecular mechanism, compounds 3b and 3g enhanced expression of the caspase-3 pro-apoptotic proteins levels besides caspase-3 gene.Review Citation - WoS: 15Citation - Scopus: 11Thioethers: an Overview(Bentham Science Publ Ltd, 2022) Han, M. Ihsan; Kucukguzel, S. GunizSpreading rapidly in recent years, cancer has become one of the causes of the highest mortality rates after cardiovascular diseases. The reason for cancer development is still not clearly understood despite enormous research activities in this area. Scientists are now working on the biology of cancer, especially on the root cause of cancer development. The aim is to treat the cancer disease and thus cure the patients. The continuing efforts for the development of novel molecules as potential anti-cancer agents are essential for this purpose. The main aim of this review was to present a survey on the medicinal chemistry of thioethers and provide practical data on their cytotoxicities against various cancer cell lines. The research articles published between 2001-2020 were consulted to prepare this review article; however, patent literature has not been included. The thioether-containing heterocyclic compounds may emerge as a new class of potent and effective anti-cancer agents in the future.