WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
Browse
3 results
Search Results
Article Citation - WoS: 2Citation - Scopus: 3Biological Activities of Etodolac-Based Hydrazone, Thiazolidinone and Triazole Derivatives on Breast Cancer Cell Lines MCF-7 and MDA-MB(Wiley, 2025) Sevinc, Sevgi Kocyigit; Cikla-Suzgun, Pelin; Tiber, Pinar Mega; Kucukguzel, S. Guniz; Orun, Oya; Güniz Küçükgüzel, Ş.In this study, several etodolac-based hydrazone, thiazolidinone, and triazole derivatives that we synthesized and characterized in our earlier research were tested against the hormone-responsive breast cell line MCF-7 and the triple-negative MDA-MB-231, as well as the murine origin fibroblast cell line L-929, at varying doses for their effects on cell viability and toxicity and for their inhibitory activity on cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) formation. Cell viability and apoptosis tests were utilized to assess the anti-cancer potential of etodolac and its derivatives after the cells were exposed to varied concentrations of synthesized compounds for three different time periods. ELISA and Western blot methods were used to detect protein levels. All synthesized compounds demonstrated higher anti-cancer activity at significantly lower doses compared to etodolac (half-maximal inhibitory concentration [IC50] of 0-50 mu M range in derivatives versus 0.5-1 mM range in etodolac). Except for SGK 242, which had a major toxic effect on all cells, the chemicals SGK 206 and SGK 217 had a twice-less impact on control murine L-929 fibroblasts. Similar to proliferation, low concentrations of SGK 206 and SGK 217 (25-50 mu M) significantly induced apoptosis in breast cancer cells but not in normal cells. Additionally, they inhibited COX-2 protein expression at 50 mu M, and SGK 206 inhibited PGE2 release more effectively than etodolac in cancer cells. The results of this study suggest that, in comparison to a healthy control group, the thiazolidinone derivative SGK 206 and the thiazolidinone derivative SGK 217 are more effective than etodolac when it comes to the breast cancer cell lines MCF-7 and MDA-MB-231. SGK 206 exhibits a low IC50 value, a distinct dose-response relationship, and strong apoptotic effects, particularly on MDA-MB-231 cells.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.