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: 14Citation - Scopus: 12Synthesis of Some Novel Hydrazide-Hydrazones Derived From Etodolac as Potential Anti-Prostate Cancer Agents(Marmara Univ, 2022) Koc, Hande Cevher; Atlihan, Irem; Mega-Tiber, Pinar; Orun, Oya; Kucukguzel, S. Guniz; Tiber, Pinar Mega(R,S)-Etodolac [1,8-diethyl-1,3,4,9-tetrahydrapyrano(3,4-b)indole-1-acetic acid] is a nonsteroidal anti-inflammatory drug that contains carboxylic acid group with the structure of pyrano[3,4-h]indole. In this study, a series of novel (R,S)-Etodolac derivatives (3a-1) bearing hydrazide-hydrazone moiety were synthesized. The structures of these compounds were characterized by spectral (H-1-NMR and FT-IR analyses) methods. All synthesized compounds were screened for anticancer activity against androgen-independent prostate adenocarcinoma (PC-3, DU-145) and androgen-dependent prostate adenocarcinoma (LNCaP) cell lines by using WST-8 colorimetric method. This method was used for cell viability and cytotoxicity analysis. Compound 3b (SGK-720) [2-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(2,6-dichlorophenyl)methylene]hydrazides] showed 10.36, 5.24, 15.53 mu M anticancer activity against PC3, DU145, LNCaP cancer cell lines, respectively. According to JC-1 mitochondrial membrane potential test and Annexin V/PI staining, 3b was found to have apoptotic effect on these cancer cells. It is concluded that compound 3b containing 2,6-dichloro substituents may be one of the candidate molecules to cope with prostate cancer.