Scopus İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/7

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  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Novel 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 İpek
    Breast 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
    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. Guniz
    In 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.