WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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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: 10Citation - Scopus: 10Novel Azole-Urea Hybrids as Vegfr-2 Inhibitors: Synthesis,<i> In</I><i> Vitro</I> Antiproliferative Evaluation And<i> In</I><i> Silico</I> Studies(Elsevier, 2023) Shirzad, Mohammad Musa; Kulabas, Necla; Erdogan, Omer; Cevik, Ozge; Dere, Damla; Yelekci, Kemal; Kucukguzel, IlkayThe vascular endothelial growth factor receptor-2 (VEGFR-2) is a receptor tyrosine kinase known to be abnormally expressed in various malignant tumors, including breast cancer, and is considered one of the most important contributors to tumor angiogenesis. Sorafenib is one of many VEGFR-2 inhibitors that have received approval for clinical use from the US FDA in recent years. Accordingly, in this study, the synthesis of two new pyrazoles, six 1,3,4-oxadiazoles, four 1,3,4-thiadiazoles, and ten 1,2,4-triazole-3-thione derivatives having structural characteristics similar to sorafenib was carried out. A preliminary screening of synthesized compounds and known inhibitors sorafenib and staurosporine at 10 mu M concentration on in vitro activity of VEGFR-2 was performed, and compounds 10c, 8a, and 11 g were identified as the most potent derivatives with% VEGFR-2 residual activities lower than 30%, and dose-dependent inhibition studies was carried out to determine the IC50 values of these inhibitors. Compound 10c was found to be the most potent inhibitor of VEGFR-2 activity with an IC50 value of 0.664 mu M. The anti-proliferative activity of synthesized derivatives was assessed against a breast carcinoma (MCF-7) cell line, a triple negative human breast adenocarcinoma (MDA-MB-231) cell line, and noncancerous fibroblast cells (L929). Compound 8a displayed superior activity when compared to sorafenib against MCF-7 (7.69 fold) and MDA-MB-231 (1.52 fold) cell lines while displaying 3.75-fold less toxicity against the normal L929 cell line. Annexin V binding assay revealed that compound 8a significantly increased early and late apoptosis in MCF-7 cells and late apoptosis and necrosis in MDA-MB-231 cells. Computational studies such as molecular docking and ADMET evaluation were performed to elucidate the binding interactions and druglikeness of the synthesized compounds. The results indicate that compound 8a could be a promising candidate for the development of a novel anti-angiogenic and anti-proliferative agent.Article Citation - Scopus: 1Protective Effects of <i>momordica Charantia</I> (bitter Melon) Against Methotrexate-Induced Kidney Damage(Bentham Science Publ Ltd, 2023) Macit, Caglar; Ozbeyli, Dilek; Cevik, Ozge; Cetin, Melisa; Sener, Goksel; Ozkan, SevilBackground Methotrexate is a cytotoxic chemotherapeutic agent that has severe side effects, such as nephrotoxicity. Momordica charantia is a bright yellow-orange fruity plant that has been shown to have antioxidant, antidiabetic, and anti-inflammatory properties. Objective This study scrutinized the protective effects of Momordica charantia extract against methotrexate-induced nephrotoxicity. Methods 24 Sprague Dawley male rats were divided into three experimental groups (8 rats in each): Control (C); Methotrexate (MTX); and Methotrexate plus Momordica charantia (MTX+MC). All rats were fed ad libitum and tap water. Methotrexate was administered at 20 mg/kg intraperitoneally as a single dose. In the MTX+MC group, MC was administered at a dose of 50mg/kg for 5 days orally. At the end of the 5th day, the rats were decapitated and kidney samples were taken to analyze glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and caspase-3 activity. Data was analyzed with GraphPad Prism 5.0. Results Findings showed that while there was a significant increase in MDA, MPO, 8-OHdG levels, and an essential reduction in GSH levels in the MTX-treated group when compared with the control group, bitter melon treatment significantly reversed MDA, MPO, and 8-OHdG levels (p< 0.001). GSH level elevation was observed in the MTX-MC group when compared to the MTX-treated group (p< 0.001). Conclusion This study showed that bitter melon is thought to have a protective effect against kidney damage caused by methotrexate. With future studies, we believe that the use of bitter melon extract as a protective agent in kidney damage caused by drug-induced oxidative damage will bring an innovative approach to treatment.Article Citation - WoS: 5Citation - Scopus: 6Hepatoprotective Effects of Parsley (petroselinum Crispum) Extract in Rats With Bile Duct Ligation(Elsevier, 2023) Ede, Seren; Özbeyli, Dilek; Erdogn, Omer; Cevik, Ozge; Kanpalta, Fatma; Ercan, Feriha; Senerg, Goksel; Şener, Göksel; Erdoğan, ÖmerBackground and study aims: This study aimed to investigate the possible protective effects of parsley extract (Petroselinum Crispum; PC) against oxidative liver damage caused by bile obstruction in rats. Material and methods: Bile duct ligation (BDL) method was used to induce liver injury in rats. The rats were divided into the three groups each consisting of 8 rats; Sham-operated control (C), bile duct ligated + saline treated (BDL), and BDL + PC treated groups. PC extract was given at a dose of 2 g/kg orally for 28 days. Aspartate amino transferase (AST), alanin amino transferase (ALT), and bilirubin levels were analyzed in sera. In order to determine free radicals in liver injury, luminol and lucigenin chemiluminescence tests used. Oxidative stress was evaluated through superoxide dismutase, glutathione, malondialdehyde, Na+/K+-ATPase and 8-hydroxy guanosine levels. Furthermore, inflammation marker myeloperoxidase, apoptosis marker caspase-3, and fibrosis markers TGF- beta and hydoxyproline were investigated. The liver tissues were also examined for histological evaluations.Results: While PC treatment decreased AST and ALT levels which increased with BDL, oxidant damage parameters also decreased with this treatment. Conclusion: The present study, which is the first research for PC extract on cholestasis induced liver damage, demonstrated that PC extract could be a potential therapeutic agent against liver fibrosis and need further studies.Article Citation - WoS: 3Citation - Scopus: 5<i>cotinus Coggygria</I> Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators(Springer, 2023) Sen, Ali; Ertas, Busra; Cevik, Ozge; Yildirim, Aybeniz; Kayali, Damla Gokceoglu; Akakin, Dilek; Sener, GokselIn traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.Article Citation - WoS: 3Citation - Scopus: 3Investigation of the Protective and Therapeutic Efficacy of <i>myrtus Communis</I> Extract in Aluminum Chloride and Dgalactose-Induced Alzheimer's Disease in Rats(Marmara Univ, 2022) Yalman, Kiibra; Sen, Ali; Cevik, Ozge; Kadioclu-Yaman, Beril; Ertas, Biiva; Yildiz, Sila; Sener, Goksel; Yaman, Beril Kadıoğlu; Kadioğlu-Yaman, BerilThis study investigated the possible protective and therapeutic effects of Myrtus communis subsp. communis ethanol extract (MC) in aluminum chloride (AlCl3) and D-galactose (D-Gal) induced Alzheimer's disease in rats. MC was orally given to rats as a protective treatment for 90 days and, in other two groups starting from the 60th day MC (100-200 mg/kg) was administered, concomitantly with AlCl3 and D-Gal. Learning and memory functions were evaluated by the behavioral tests. Biological activities of MC treatment were examined in hippocampal tissues by ELISA tests. D-Gal and AlCl3-treated rats showed increased amyloid beta (A ss) and 8-hydroxy-2-deoxyguanosine (8OHdG) levels, acetylcholinesterase activity and decreased neprilysin, Na+-K+ATPase and SOD levels in parallel with a decrease in Novel Object Recognition Test, Morris Water Maze and Passive Avoidance Test scores. On the other hand, MC administration reversed the behavioral impairments and improved learning and memory. Moreover, MC treatment decreased A ss and 8-OHdG levels and acetylcholinesterase activity and increased neprilysin levels, Na+-K+ATPase and SOD levels. Our results suggest that MC has beneficial effects on cognitive and neuronal functions through its anticholinesterase and antioxidant properties.