PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/8
Browse
2 results
Search Results
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. GunizIn 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.Article Citation - WoS: 5Citation - Scopus: 5Paricalcitol Protects Against Hydrogen Peroxide-Induced Injury in Endothelial Cells Through Suppression of Apoptosis(Frontiers Media Sa, 2023) Koksal, Muhammet Murat; Sekerler, Turgut; Cevik, Ozge; Sener, AzizeThe vascular endothelium is one of the main targets of oxidative stress which plays an important role in the pathophysiology of vascular damage. Recent studies show that vitamin D can positively regulate endothelial functions in various chronic diseases and in cases of increased oxidative stress. In our study, we investigated the restorative and protective potentials of paricalcitol which is frequently used in patients with chronic renal failure, a vitamin D analogue, in human umbilical vein endothelial cells (HUVEC) before and after H2O2-induced oxidative stress. Paricalcitol treatment after the oxidative stress induced by H2O2 increased cell viability in endothelial cells depending on the dose that was used. While paricalcitol (500 nM) decreased caspase-3 activity and mitochondrial membrane potential loss, it increased nitric oxide (NO) production and reduced glutathione (GSH) levels. Paricalcitol treatment before oxidative stress increased cell viability. It increased NO production and mitochondrial membrane potential while significantly reducing caspase-3 activity. While paricalcitol caused a significant inhibition of protein disulfide isomerase (PDI) reductase activity in healthy endothelial cells, it did not cause a significant change on the PDI reductase activity under oxidative stress conditions. Present study showed that paricalcitol has restorative and protective effects on endothelial cells against oxidative injury, but these effects occur at high concentrations of paricalcitol.