WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article New Diclofenac Hydrazones: Design, Synthesis, in Silico Studies and Anticancer Evaluation Against Breast Cancer(Elsevier, 2026) Birgul, Kaan; Oktay, Lalehan; Bekci, Hatice; Cikla-Suzgun, Pelin; Durdagi, Serdar; Kucukguzel, S. GunizBreast cancer remains one of the most prevalent and lethal malignancies among women, highlighting the urgent need for novel therapeutic strategies that can overcome resistance mechanisms. The p38 alpha mitogen-activated protein kinase (MAPK14) plays a key role in inflammation-associated oncogenic signaling, making it an attractive molecular target for drug development. In this study, a novel series of diclofenac-based hydrazone derivatives (4a-4o) were designed, synthesized, and characterized using FT-IR, 1H- and 13C-NMR spectroscopy, thin-layer chromatography, and elemental analysis. Computational target profiling using SwissTargetPrediction identified MAPK14 as the primary predicted target. Molecular docking against the MAPK14 crystal structure (PDB ID: 1WBS) revealed high binding affinities (-11.41 to -8.34 kcal/mol), supported by MM/GBSA free energy calculations and molecular dynamics simulations, which confirmed stable ligand-protein interactions through hydrogen bonding with Asp168 and Glu71. In vitro cytotoxicity assays on MCF-7 (luminal A) and MDA-MB-231 (triple-negative) breast cancer cell lines demonstrated low-micromolar IC50 values, with compounds 4c, 4d, and 4e showing the strongest activity (2.1-4.5 mu M), surpassing the reference drug Tamoxifen. Overall, the results indicate that diclofenac hydrazones represent promising candidates anticancer properties through MAPK14 inhibition, providing a foundation for the development of next-generation therapeutics against breast cancer.Article Citation - WoS: 2Citation - Scopus: 3Biological Activities of Etodolac-Based Hydrazone, Thiazolidinone and Triazole Derivatives on Breast Cancer Cell Lines MCF-7 and MDA-MB(Wiley, 2025) Sevinc, Sevgi Kocyigit; Cikla-Suzgun, Pelin; Tiber, Pinar Mega; Kucukguzel, S. Guniz; Orun, Oya; Güniz Küçükgüzel, Ş.In this study, several etodolac-based hydrazone, thiazolidinone, and triazole derivatives that we synthesized and characterized in our earlier research were tested against the hormone-responsive breast cell line MCF-7 and the triple-negative MDA-MB-231, as well as the murine origin fibroblast cell line L-929, at varying doses for their effects on cell viability and toxicity and for their inhibitory activity on cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) formation. Cell viability and apoptosis tests were utilized to assess the anti-cancer potential of etodolac and its derivatives after the cells were exposed to varied concentrations of synthesized compounds for three different time periods. ELISA and Western blot methods were used to detect protein levels. All synthesized compounds demonstrated higher anti-cancer activity at significantly lower doses compared to etodolac (half-maximal inhibitory concentration [IC50] of 0-50 mu M range in derivatives versus 0.5-1 mM range in etodolac). Except for SGK 242, which had a major toxic effect on all cells, the chemicals SGK 206 and SGK 217 had a twice-less impact on control murine L-929 fibroblasts. Similar to proliferation, low concentrations of SGK 206 and SGK 217 (25-50 mu M) significantly induced apoptosis in breast cancer cells but not in normal cells. Additionally, they inhibited COX-2 protein expression at 50 mu M, and SGK 206 inhibited PGE2 release more effectively than etodolac in cancer cells. The results of this study suggest that, in comparison to a healthy control group, the thiazolidinone derivative SGK 206 and the thiazolidinone derivative SGK 217 are more effective than etodolac when it comes to the breast cancer cell lines MCF-7 and MDA-MB-231. SGK 206 exhibits a low IC50 value, a distinct dose-response relationship, and strong apoptotic effects, particularly on MDA-MB-231 cells.Article Investigation of the Printability of Ethyl 2-[4 on Coated and Uncoated Papers](Wiley, 2025) Akgul, Ahmet; Kucukguzel, S. Guniz; Oktav, Mehmet; Rollas, SevimThere is a growing demand in the printing industry for pigment-based inks with excellent lightfastness and rub resistance qualities. In this work, a novel ink with the formulation ethyl 2-[4-(1,3,4-oxadiazole-2(3H)-thione-5-yl)phenylhydrazono]-3-oxobutyrate (OXKT) was prepared as a pigment and its printability was investigated for use in printing. The OXKT was synthesised, characterised then printed on uncoated and gloss-coated papers and Bristol cardboard. Physical tests and spectrophotometric measurements were carried out to determine the technical characteristics of the printed ink. Additionally, print quality, ink density and gloss were evaluated. The results showed that the proposed ink with the OXKT compound had acceptable rub resistance. Also, the gloss and light fastness values exceeded the acceptable rates for the printing industry because of their colour differences. However, more research needs to be conducted to improve light performance. Nevertheless, it is still possible for use in applications that do not stipulate strict light fastness values.Article Citation - WoS: 2Citation - Scopus: 1Synthesis and Investigation of Cytotoxic Effects of Compounds Derived From Flurbiprofen(Elsevier, 2023) Gokoglan, Ecem; Dere, Damla; Bedir, Ipek; Yelekci, Kemal; Telci, Dilek; Kucukguzel, S. GunizNew flurbiprofen derivatives containing 1,2,4-triazoline-5-thione (4) and thioethers (5a-r) were synthesized in this study. The structures of synthesized compounds were characterized by spectral methods (FT-IR, 1H NMR, 13C NMR) and 19F NMR (only compound 5l), besides elemental analysis. In addition, molecular binding of these compounds to the human methionine aminopeptidase 2 enzyme was performed using AutoDock 4.2, the software product of the research, computationally. All synthesized compounds were evaluated for cytotoxic effect against MDA-MB231 triple-negative breast cancer cell line by using WST-1 Cell Viability and Proliferation assay. Doxorubicin is in the anthracycline class and is an antineoplastic agent. It is used to provide regression in common neoplastic conditions such as breast carcinoma. Due to the cardiovascular side effects of doxorubicin, a combination study was conducted with the (& PLUSMN;)(R,S)-3-{1-[2-fluoro-(1,1 & PRIME;-biphenyl)-4-yl]ethyl}-4-methyl-5-{[2(trifluoromethyl)benzyl]thio}-4H-1,2,4-triazole (5l) with promising cytotoxic effects. As a result of the combination, it was shown as 7% MDA-MB231 cell viability. Therefore, based on the evaluations, a better cytotoxic effect was achieved with the 5l combination depending on the low dose of doxorubicin.Article Citation - WoS: 13Citation - Scopus: 14Synthesis, Antimicrobial Evaluation and Molecular Modeling Studies of Novel Thiosemicarbazides/Semicarbazides Derived From <i>p</I>-aminobenzoic Acid(Elsevier, 2022) Han, M. Ihsan; Ince, Ufuk; Gunduz, Miyase Gozde; Coskun, G. Pelin; Birgul, Kaan; Dogan, Senguel Dilem; Kucukguzel, S. Guniz; İhsan Han, M.The development of novel antimicrobial agents is critical to combat life-threatening drug-resistant bacterial and fungal pathogens. In the present study, a new series of p-aminobenzoic acid (PABA) derivatives carrying thiosemicarbazide/semicarbazide moiety were designed, synthesized, and studied for their antimicrobial activity. The target molecules (3a-f, 4a-f) were achieved by the reaction of 4aminobenzohydrazide, obtained from PABA, and various phenyl isothiocyanates/isocyanates. Following structural characterization by spectroscopic methods (H-1 NMR, C-13 NMR, FT-IR, and LC-MS analyses), the synthesized compounds were tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and their clinical isolates. Thiosemicarbazides with lipophilic substituents on the phenyl ring were identified as the most active compounds in this series. Among the studied molecules, compound 3e, thiosemicarbazide derivative with trifluoromethyl groups on the phenyl moiety, showed the best antimicrobial activity. Physicochemical parameters of the compounds were computed to predict the drug-likeness of the title compounds. Finally, molecular docking studies were performed in the allosteric binding pocket of ?-alanine: ?-alanine ligase (Ddl) to explain the potential antibacterial activity mechanism of 3e against S. aureus strains . (C) 2022 Elsevier B.V. All rights reserved.Article Citation - WoS: 18Citation - Scopus: 20Design, Synthesis and Anticancer Activity Studies of Novel 4-Butylaminophenyl Hydrazide-Hydrazones as Apoptotic Inducers(Pergamon-elsevier Science Ltd, 2022) Han, M. Ihsan; Baysal, Ozge Deniz Yesil; Basaran, Guzide Satir; Sezer, Gulay; Telci, Dilek; Kucukguzel, S. Guniz; Yeşil Baysal, Özge DenizIn this study, a series of the novel Tetracaine derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (H-1-C-13 NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds (2a-1) were screened for anticancer activity against human hepatocellular carcinoma (HepG2) and lung carcinoma (A549) cell lines. Against HepG2 and A549 cell lines, among the synthesized compounds, 4-(Butylamino)-N'-[(2,4-dichlorophenyl)methylidene]benzohydrazide (2i) demonstrated the most potent anticancer activity with IC50 values 28 and 7 mu M, respectively. Possible cytotoxic effects of compounds (2a-1) on both normal human lung fibroblast (MCR-5) and normal human dermal fibroblast (HDF) cell lines were assessed. Inhibition of anti-apoptotic protein Bax and Bcl-2 was investigated in HepG2 and A549 cells treated with compound 2i using qRT-PCR. Apoptosis was also detected by Annexin V studies. The flow cytometric analysis results showed that compound 2i treatment of HepG2 and A549 cells significantly increased apoptotic cell populations while decreasing viabilities in these carcinomas in a dose-dependent manner after 72 h of incubation. (C) 2022 Elsevier Ltd. All rights reserved.Article Citation - WoS: 9Citation - Scopus: 10Synthesis and Molecular Modeling of Metap2 of Thiosemicarbazides, 1,2,4-Triazoles, Thioethers Derived From (s)-Naproxen as Possible Breast Cancer Agents(Elsevier, 2022) Birgul, Kaan; Uba, Abdullah Ibrahim; Cuhadar, Ozan; Sevinc, Sevgi Kocyigit; Tiryaki, Selen; Tiber, Pinar Mega; Kucukguzel, S. Guniz; Güniz Küçükgüzel, Ş.New thiosemicarbazides (3, 5-6), 1,2,4-triazoles (14-15) and thioethers (22-68) from derived (S)-Naproxen were synthesized in this study. The structure of these compounds were elucidated by spectral (FT-IR, H-1 NMR, C-13 NMR) methods, besides elemental analysis and TLC. The molecular binding of the compounds on MetAP-2 was performed. Anticancer effects of the synthesized compounds were studied by using MTT assay method on MCF-7 (includes oestrogene and progesterone receptors) and MDA-MB-231 (lacks estrogen and progesterone receptors) adenocarcinoma cell lines at 0, 10, 25, 50, 75 and 100 mu M concentrations for 24 h. The IC(50 )values of novel (S)-Naproxen derivatives were determined between from 5 to 100 mu M on MCF-7 breast cancer cell line and MDA-MB-231 cell lines. The apoptotic activity of selected compounds 22 and 42 were first analyzed by Annexin V staining using Tali Image-Based Cytometer. Mitochondrial membrane potential changes determined in fluorescence plate reader following JC-1 stain for compounds 22 and 42 in MCF-7 and MDA-MB-231 cells. The effect of these compounds on the cell viability 4T1 mouse mammary tumor cell line was tested at 1 to 5 times of calculated IC50 value (IC(50)x1, IC(50)x2, IC(50)x3, IC(50)x4, and IC(50)x5). Next in order to determine the toxicity of the combination of compound 51 and Docetaxel, WST-1 cell viability and proliferation assay was performed with 4T1. (C) 2022 Elsevier B.V. All rights reserved.