WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Citation - WoS: 2Citation - Scopus: 2Evaluation of Hydrazide-Hydrazone and 4-Thiazolidinone Derivatives of Etodolac as Potential Anticancer Agents in Leukemia Cells(Bentham Science Publ Ltd, 2024) Tiber, Pinar Mega; Averbek, Sera; Sevinc, Sevgi Kocyigit; Kilinc, Olca; Suzgun, Pelin Cikla; Kucukguzel, S. Guniz; Orun, Oya; Koçyiğit Sevinç, SevgiBackground Nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used for their anti-inflammatory and analgesic properties, have also been found to prevent cancer. (+/-)(R,S) Etodolac is an NSAID that belongs to the class of cyclooxygenase-2 inhibitors. Various derivatives of etodolac are synthesized to boost its anti-proliferative action and lessen its potential negative effects. In our earlier studies, some novel derivatives of etodolac exhibited stronger cytotoxic effects on prostate cell lines and had similar effects on leukemia cells in pre-screening experiments.Objective Using the K562 leukemia cell line as a model, we sought to investigate the anti-cancer properties of a hydrazide-hydrazone derivative (SGK-205) and a 4-thiazolidinone derivative of etodolac (SGK-216).Materials and Methods In the current investigation, SGK-205 and SGK-216 compounds were administered to K562 cells for 24 and 48 hours at concentrations of 10, 25, 50, 75 and 100 mu M. Cell viability was assessed using the MTT test, and apoptosis by Annexin V-PI staining and mitochondrial membrane potential assays, together with mRNA expressions of apoptotic proteins. The levels of the proteins, HER2 and COX2, were also examined to evaluate COX2 inhibitory capacity.Results In K562 cells, there was a definite dose-dependent response to SGK-205 and SGK-216 compounds. Results from MTT viability tests, together with mitochondrial membrane potential measurements and Annexin V-PI staining, revealed that SGK-216 and SGK-205 significantly outperformed etodolac in terms of their apoptotic and anti-proliferative activities. The concentration range of 10-20 mu M for both chemicals was sufficient to start biological responses. Apoptosis was also investigated through the expressions of pro- and anti-apoptotic proteins. Additionally, gene expression research demonstrated SGK-205 to be a beneficial substitute to etodolac in lowering COX-2 and human epidermal growth factor receptor-2 (HER2) expression.Conclusion Our data indicated both derivatives to have higher anti-proliferative and apoptotic effects compared to etodolac. An overall assessment highlighting apoptotic induction potential, acceptable toxicity levels, a consistent dose-response relationship, and COX2 inhibitory actions, in particular, indicated SGK-205 as a viable novel therapeutic.Article Citation - WoS: 9Citation - Scopus: 10Synthesis and Molecular Modeling of Metap2 of Thiosemicarbazides, 1,2,4-Triazoles, Thioethers Derived From (s)-Naproxen as Possible Breast Cancer Agents(Elsevier, 2022) Birgul, Kaan; Uba, Abdullah Ibrahim; Cuhadar, Ozan; Sevinc, Sevgi Kocyigit; Tiryaki, Selen; Tiber, Pinar Mega; Kucukguzel, S. Guniz; Güniz Küçükgüzel, Ş.New thiosemicarbazides (3, 5-6), 1,2,4-triazoles (14-15) and thioethers (22-68) from derived (S)-Naproxen were synthesized in this study. The structure of these compounds were elucidated by spectral (FT-IR, H-1 NMR, C-13 NMR) methods, besides elemental analysis and TLC. The molecular binding of the compounds on MetAP-2 was performed. Anticancer effects of the synthesized compounds were studied by using MTT assay method on MCF-7 (includes oestrogene and progesterone receptors) and MDA-MB-231 (lacks estrogen and progesterone receptors) adenocarcinoma cell lines at 0, 10, 25, 50, 75 and 100 mu M concentrations for 24 h. The IC(50 )values of novel (S)-Naproxen derivatives were determined between from 5 to 100 mu M on MCF-7 breast cancer cell line and MDA-MB-231 cell lines. The apoptotic activity of selected compounds 22 and 42 were first analyzed by Annexin V staining using Tali Image-Based Cytometer. Mitochondrial membrane potential changes determined in fluorescence plate reader following JC-1 stain for compounds 22 and 42 in MCF-7 and MDA-MB-231 cells. The effect of these compounds on the cell viability 4T1 mouse mammary tumor cell line was tested at 1 to 5 times of calculated IC50 value (IC(50)x1, IC(50)x2, IC(50)x3, IC(50)x4, and IC(50)x5). Next in order to determine the toxicity of the combination of compound 51 and Docetaxel, WST-1 cell viability and proliferation assay was performed with 4T1. (C) 2022 Elsevier B.V. All rights reserved.