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 - Scopus: 1Synthesis and Anti-Hcv Activity of Novel 5-Arylmethylene Derivatives Via Suppression of Ns5b Polymerase and Cox-2(Elsevier, 2024) Kulabas, Necla; Lee, Jin-Ching; Ozakpinar, Ozlem Bingol; Kucukguzel, Ilkay; Bingöl Özakpınar, ÖzlemHepatitis C (HCV) is a viral infection that leads to forms of acute and chronic liver disease, including cirrhosis (scarring of the liver) and liver cancer. The World Health Organization (WHO) estimated in 2019 that approximately 290,000 people died from hepatitis C (mostly from cirrhosis and hepatocellular carcinoma). Directacting antiviral drugs (DAAs) can cure more than 95% of individuals with hepatitis C infection, while research on the discovery of new antiviral agents is still ongoing. The Hepatitis C virus (HCV) can cause various biochemical changes in liver cells, and some of these changes are associated with the COX-2 enzyme. The identification of its role in promoting growth in liver cells as well as its involvement in various cancer types, including hepatocellular carcinoma, has made COX-2 an important target in the development of new agents effective against HCV. In this study, thirty-six new 5-arylmethylene-2-imino-1,3-thiazolidin-4-one derivatives (5a-s, 6a-s) were synthesized through Knoevenagel condensation of 2-[(4-substitutedpyridin-2-yl)imino]-1,3thiazolidin-4-one derivatives with various aldehydes. Structures of the synthesized compounds were elucidated by the use of spectral and chromatographic techniques, besides elemental analyses. Four compounds were selected for further studies as they were found to suppress the NS5B protein with anti-HCV activity using the Western Blotting method. The selected compounds 5o, 6m, 6r, and 6s inhibited HCV with EC50 values of 8.0 +/- 0.2 mu M, 13.9 +/- 0.45, 9.2 +/- 0.2 mu M, and 12.1 +/- 0.1 mu M, respectively. It was determined that these compounds reduced HCV-induced COX-2 promoter activity in Ava5 cells compared to Huh7 cells. The antiviral effects of the compounds were also investigated on DENV, closely related to HCV due to sharing certain biological, structural, and mechanical properties throughout their life cycles. However, no significant effect was observed in the preliminary screening study, indicating the compounds' specificity for HCV. Considering the relationship between HCV, DENV, and COX-2, the compounds' COX-1 and COX-2 enzyme inhibition potentials were investigated both in vitro and in silico. Compounds 6d, 6e, 6f, and 6m, which exhibited high selective COX-2 inhibition, were discussed for their interactions with the active site. Our study revealed that our target compounds suppressed COX-2 both at the protein level and through enzyme inhibition, thus providing promising findings for the discovery of new anti-HCV effective COX-2 inhibitors.