WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Citation - WoS: 2Citation - Scopus: 2Novel Triazole-Urea Hybrids as Promising EGFR Inhibitors: Synthesis, Molecular Modeling and Antiproliferative Activity Studies Against Breast Cancer(Elsevier, 2025) Ture, Asli; Gulcan, Mehmet Metehan; Birgul, Serap Ipek Dingis; Erdogan, Oguz; Erdogan, Omer; Tuncay, Fulya Oz; Kucukguzel, Ilkay; Öz Tuncay, Fulya; Dingiş Birgül, Serap İpekBreast cancer is the second leading cause of mortality among women globally. In this study, novel promising urea derivatives containing a 4-phenyl-5-sulphanylidene-4,5-dihydro-1H-1,2,4-triazole group were synthesized and evaluated for their biological activities against breast cancer. The cytotoxicity and apoptotic profiles of these compounds were assessed on the MCF7 breast cancer cell line and the L929 fibroblast cell line. Compound 5c exhibited the strongest anticancer activity against MCF7 cells with an IC50 value of 56.97+4.22 mu M, while it showed significantly lower cytotoxicity against L929 cells (IC50 = 1651+18.39 mu M). Compound 5c also induced early apoptosis in MCF7 cells, with an apoptosis rate of 18.40% and 5.28%, respectively. Additionally, the EGFR inhibitory activities of the synthesized compounds were evaluated, with compound 5i demonstrating the most potent EGFR inhibition, showing an IC50 value of 35.1 nM. These results suggest that compound 5c likely exerts its anticancer effects through mechanisms other than EGFR inhibition, while compound 5i has significant potential as an effective EGFR inhibitor. Molecular modeling studies were conducted to suggest putative binding interactions of compounds 5d, 5e and 5i with wildtype hEGFR. Further studies are warranted to explore their activity against other cancer types.Article Citation - WoS: 1Citation - Scopus: 2Glyphosate and AMPA-Induced Apoptosis and Epigenetic Alterations in HepG2 Cells: Upregulation of P53-BAX-CASP Pathways(Pergamon-Elsevier Science Ltd, 2025) Mehtiyev, Tugrul; Guler, Zeynep Rana; Aktan, Elif; Ozden, SibelGlyphosate and its metabolite aminomethylphosphonic acid (AMPA) are environmental contaminants with potential toxic effects. This study aimed to investigate apoptosis and epigenetic alterations induced by glyphosate and AMPA in HepG2 cells. The IC50 values for glyphosate and AMPA were 6.19 mM and 8.13 mM, respectively, following 24 h exposure; mechanistic assays were conducted at sub-cytotoxic concentrations (50-500 mu M). Annexin V/PI flow cytometry revealed that AMPA significantly increased early apoptosis (up to 116 %, p < 0.001), while glyphosate elevated late apoptosis (up to 145 %, p < 0.001). Gene expression analysis showed significant upregulation of p53 (>= 1.49-fold), BAX (>= 1.82-fold), CASP3 (>= 1.37-fold), and CASP9 (>= 1.83-fold), with no significant change in BCL2. Epigenetic analysis indicated that both glyphosate and AMPA increased global DNA methylation, with fold changes ranging from 1.43 to 1.62-fold at concentrations of 100-250 mu M (p < 0.05). DNA methyltransferase genes DNMT1 (>= 2.44-fold), DNMT3A (>= 1.65-fold), and DNMT3B (>= 1.65-fold) were upregulated. Additionally, histone modification profiling showed elevated levels of H3K27me3, H3K9me3, and H3K9ac (p < 0.05), alongside increased expression of G9a (>= 1.64-fold), EZH2 (>= 2.14-fold), SETD1B (>= 2.15-fold), HAT1 (>= 2.40-fold), and SIRT1 (>= 2.57-fold), and downregulation of SUV39H1 (>= 0.27-fold). These findings reveal the molecular mechanisms of glyphosate and AMPA toxicity, linking apoptosis to epigenetic alterations and enhancing understanding of their risks.Article Citation - WoS: 4Citation - Scopus: 4Synthesis of Novel Triazole-Urea Hybrids and Their Antiproliferative Activity Against Pancreatic Cancer Through Suppression of Eef2k and Induction of Apoptosis(Elsevier, 2024) Tuere, Asli; Ozdemir, Burcu; Cece, Onur; Armagan, Guliz; Erdogan, Mumin Alper; Erdogan, Omer; Kucukguzel, Ilkay; Türe, AslıPancreatic cancer is one of the deadliest cancers with its highly aggressive and metastatic character and there is a huge unmet need for new drugs treating pancreatic cancer. In the present study, a series of 1,2,4-triazole-urea conjugates have been designed and synthesized as novel candidates of antiproliferative agents against pancreatic cancer cells. Among them, compounds 33, 34, 35 and 38 possesing IC50 values between 0.231 and 0.488 mu M against PANC-1 cells demonstrated the highest anti-proliferative activity. These compounds presenting the highest antiproliferative activity were evaluated for further biological studies. The same four compounds inhibited colony formation in pancreatic cancer cells dose dependently. Western blot study on the selected compounds showed that compounds 33 and 38 significantly reduced eEF2K protein levels in cancer cells. These compounds displayed an effective eEF2K activity suppression by down-regulated levels of unphosphorylated eEF2 in PANC-1 cells. Compounds 33, 34, 35 and 38 were also demonstrated to induce apoptosis and activate caspase 3/7. In silico studies were performed to predict the druggability and ADMET/ properties of the active molecules. In summary, 1,2,4-triazole-urea conjugates developed in this study represent a novel and promising lead structure with anticancer activity against pancreatic cancer achieved through eEF2K activity suppression. Compounds being referred to are the first "triazole-urea hybrid" molecules found to be effective against pancreatic cancer.Article Citation - WoS: 18<i>petroselinum Crispum</I> Extract Ameliorates Scopolamine-Induced Cognitive Dysfunction: Role on Apoptosis, Inflammation and Oxidative Stress(Tsinghua Univ Press, 2022) Sener, Goksel; Karakadioglu, Gozde; Ozbeyli, Dilek; Ede, Seren; Yanardag, Refiye; Sacan, Ozlem; Aykac, AsliThis study was designed to investigate whether Petroselinum crispum (PC) extract has protective effects on the brain in the scopolamine-induced Alzheimer's disease (AD) rut model. The rats were divided into; control, scopolamine (1 mg/kg, i.p.), galantamine (1.5 mg/kg, i.p.) and PC extract (2 g/kg, p.o.)-treated scopolamine groups. On day 14, the novel object recognition test (NORT) and Morris water maze test (MWMT) were performed and then the rats were sacrificed. Scopolamine-induced cognitive impairments observed in the NORT and MWMT, significantly improved with PC extract and galantamine treatments. Scopolamine reduced M, receptor expression, Bcl-2/Bax ratio, and glutathione levels in the hippocampus and frontal cortex, while malondialdehyde levels, caspase-3/9 expressions, and acetylcholinesterase (AChE) activity were found to be increased. On the other band, PC and galantamine treatments reversed these changes. In conclusion, PC extract has shown an ameliorative effect on the spatial and recognition memory, M-1 receptor expression, apoptosis, oxidative stress, and increased AChE activity. Thus, it was concluded that PC could prevent AD-like conditions and can be used as a functional food. However, since animal models do not completely mimic those of humans, based on the data obtained in this study, the importance of PC on human AD should be demonstrated in future studies. (C) 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.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.