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 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: 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.