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: 11Citation - Scopus: 11Synthesis and Biological Evaluation of Novel Aryloxyacetic Acid Hydrazide Derivatives as Anticancer Agents(Taylor & Francis inc, 2021) Senkardes, Sevil; Erdogan, Omer; Cevik, Ozge; Kucukguzel, S. GunizIn our continuing search for new anticancer agents, herein we report the synthesis of 2-(4-chloro-3-methylphenoxy)-N'-[(aryl)methylidene]acetohydrazides 3a-j and the evaluation of their anticancer activities on cell viability, morphological changes and caspase-3 activity in cancer cell lines including gastric cancer (MKN45), cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells. 2-(4-chloro-3-methylphenoxy)-N'-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g presented the strongest growth inhibition against MKN45 gastric cancer cell lines with the IC50 value of 1.471 +/- 0.23 mu M. Moreover, compounds 3b and 3g showed high potency against the HeLa and MDA-MB-231 cell lines having IC50 in the range of 2.38-9.72 mu M. These compounds are more selective for the tested human cancer cells than for the mouse fibroblast cell line (NIH/3T3). As a result of the studies conducted in order to understand the molecular mechanism, compounds 3b and 3g enhanced expression of the caspase-3 pro-apoptotic proteins levels besides caspase-3 gene.