Küçükgüzel, Şükriye Güniz
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Kucckguzel, S. Guniz
Kucukguzel, S. Gueniz
Kucukguzel, S. Guniz
Küçükgüzel, Ş.G.
Kucukguzel, S. Gueniz
Kucukguzel, S. Guniz
Küçükgüzel, Ş.G.
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guniz.kucukguzel@fbu.edu.tr
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Scholarly Output
18
Articles
17
Citation Count
105
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0
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Now showing 1 - 10 of 18
Article Citation Count: 0Evaluation of Hydrazide-Hydrazone and 4-Thiazolidinone Derivatives of Etodolac as Potential Anticancer Agents in Leukemia Cells(Bentham Science Publ Ltd, 2024) Küçükgüzel, Şükriye Güniz; Averbek, Sera; Sevinc, Sevgi Kocyigit; Kilinc, Olca; Suzgun, Pelin Cikla; Kucukguzel, S. Guniz; Orun, Oya; Eczacılık Meslek Bilimleri BölümüBackground 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 Count: 1Molecular Modelling Studies To Suggest Novel Scaffolds Against Sars-Cov Target Enzymes(Marmara Univ, 2021) Küçükgüzel, Şükriye Güniz; Kucukguzel, S. Guniz; Akdemir, Atilla; Eczacılık Meslek Bilimleri BölümüIn this study, molecular modelling study of previously synthesized compounds against SARS-CoV-2 target enzyme was performed. A subset of 156 compounds from an in-house database has been subjected to molecular modelling studies against the SARS-CoV-2 ADP-ribose phosphatase (ADRP, NSP3), Papain-like protease (PLpro), and uridine specific endoribonuclease (NSP15) enzymes. We have identified one compound that is expected to inhibit the SARS-CoV-2 ADRP enzyme and one compound that is expected to inhibit the NSP15 enzyme.Article Citation Count: 2Synthesis, Antimicrobial Properties and in Silico Studies of Aryloxyacetic Acid Derivatives With Hydrazone or Thiazolidine-4 Scaffold(Taylor & Francis inc, 2023) Küçükgüzel, Şükriye Güniz; Kart, Didem; Bebek, Bilge; Gunduz, Miyase Gozde; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüIn this work, twenty hydrazide-hydrazone and 4-thiazolidinone derivatives were synthesized starting from m-cresol. Antimicrobial evaluation was carried out by microdilution method against Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria and Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria, and three pathogenic fungi Candida albicans, Candida parapsilosis and Candida krusei. Some compounds possessed considerable antimicrobial properties against the tested microorganisms, particularly against E. coli. 4-Thiazolidinones containing 3-methoxyphenyl and 3,5-dichlorophenyl moieties (4h and 4i) were found to be the most active derivatives with MICs of 2 mu g/mL against E. coli. N'-[(3,5-dichlorophenyl)methylidene]-2-(3-methylphenoxy)acetohydrazide (3i) also displayed antifungal activity against Candida krusei that was comparable to fluconazole. Calculated drug-likeness and ADMET parameters of the most active compounds confirmed their potential as antimicrobial drug candidates. Molecular docking investigations were carried out in the thiamine diphosphate-binding site of pyruvate dehydrogenase multienzyme complex E1 component (PDHc-E1) to clarify the potential antibacterial mechanism against E. coli. The results showed the potential and importance of developing new hydrazones and 4-thiazolidinones that would be effective against microbial strains. Communicated by Ramaswamy H. SarmaArticle Citation Count: 6Design, Synthesis, and in Vitro and in Vivo Anticancer Activity Studies of New (s)-naproxen Thiosemicarbazide/1,2,4-triazole Derivatives(Royal Soc Chemistry, 2022) Küçükgüzel, Şükriye Güniz; Tunc, Cansu Umran; Atalay, Pinar; Erdogan, Omer; Unal, Gokhan; Bozkurt, Mehmet; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüIn this study, a series of novel (S)-Naproxen derivatives bearing a thiosemicarbazide/1,2,4-triazole moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (H-1-C-13 NMR, FT-IR, and HR-MS analyses) methods. All of the synthesized compounds (3a-m, 4a-j) were screened for anticancer activity against human breast cancer cell line MDA-MB-231. Among them, (S)-4-(2,4-dichlorophenyl)-5-[1-(6-methoxynaphthalen-2-yl)ethyl]-4H-1,2,4-triazole-3-thione (4b) showed the most potent anticancer activity with a good selectivity (IC50= 9.89 +/- 2.4 mu M). Inhibition of anti-apoptotic protein Bcl-2 was investigated in MDA-MB-231 cells treated with compound 4b using Western Blotting. Apoptosis was also detected by AO/EB and JC-1 staining. Furthermore, activation of caspase-3 enzyme activity demonstrated apoptosis. The flow cytometric analysis results showed that compound 4b decreases the number of cells in the G2/M phase and increases the cells in the S phase in a dose-dependent manner. The anticancer activity of compound 4b was also investigated. In the Ehrlich acid tumor model, a well-validated in vivo ectopic breast cancer model, compound 4b had anticancer activity and reduced the tumor volume at both low (60 mg kg(-1)) and high (120 mg kg(-1)) doses in mice, according to our in vivo results.Article Citation Count: 8Synthesis, Antimicrobial Evaluation and Molecular Modeling Studies of Novel Thiosemicarbazides/Semicarbazides Derived From p-aminobenzoic Acid(Elsevier, 2022) Küçükgüzel, Şükriye Güniz; Ince, Ufuk; Gunduz, Miyase Gozde; Coskun, G. Pelin; Birgul, Kaan; Dogan, Senguel Dilem; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüThe development of novel antimicrobial agents is critical to combat life-threatening drug-resistant bacterial and fungal pathogens. In the present study, a new series of p-aminobenzoic acid (PABA) derivatives carrying thiosemicarbazide/semicarbazide moiety were designed, synthesized, and studied for their antimicrobial activity. The target molecules (3a-f, 4a-f) were achieved by the reaction of 4aminobenzohydrazide, obtained from PABA, and various phenyl isothiocyanates/isocyanates. Following structural characterization by spectroscopic methods (H-1 NMR, C-13 NMR, FT-IR, and LC-MS analyses), the synthesized compounds were tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and their clinical isolates. Thiosemicarbazides with lipophilic substituents on the phenyl ring were identified as the most active compounds in this series. Among the studied molecules, compound 3e, thiosemicarbazide derivative with trifluoromethyl groups on the phenyl moiety, showed the best antimicrobial activity. Physicochemical parameters of the compounds were computed to predict the drug-likeness of the title compounds. Finally, molecular docking studies were performed in the allosteric binding pocket of ?-alanine: ?-alanine ligase (Ddl) to explain the potential antibacterial activity mechanism of 3e against S. aureus strains . (C) 2022 Elsevier B.V. All rights reserved.Article Citation Count: 0Synthesis and Biological Evaluation of New 4-Thiazolidinone Derivatives of Flurbiprofen(Acg Publications, 2023) Küçükgüzel, Şükriye Güniz; Senkardes, Sevil; Gurboga, Merve; Ozakpinar, Ozlem Bingol; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüIn this study, the synthesis and characterization of 2-(2-fluorobiphenyl-4-yl)-N '-[(substituted methylene]propanehydrazides (3a-s) and 2-(2-fluoro-[1,1'-biphenyl]-4-yl)-N-(5-methyl-2-(substituted aryl)-4oxothiazolidin-3-yl)propanamides (4a-s) are described and also the antiproliferative effect of the compounds on HT 29, HeLa, A549 and MCF-7 cancer cell lines is investigated. Additionally, mouse embryonic fibroblast cells NIH3T3 were also evaluated to determine the selectivity. The results showed that the identified compounds did not cause any toxicity against NIH3T3 cell line. Moreover, N-(2-(3,5-Bis(trifluoromethyl)phenyl)-5-methyl-4-oxothiazolidin-3-yl)-2-(2-fluoro-[1,1'-biphenyl]-4-yl)propanamide (4h) had the most growth inhibitory effect (55.97% inhibition) on HT-29 colorectal adenocarcinoma cell line. The results obtained from the study show that the compound 4h, which has no cytotoxic effect on normal cells, may be an alternative in the treatment of colon cancer.Article Citation Count: 1Synthesis and Investigation of Cytotoxic Effects of Compounds Derived From Flurbiprofen(Elsevier, 2023) Gökoğlan, Ecem; Küçükgüzel, Şükriye Güniz; Bedir, Ipek; Yelekci, Kemal; Telci, Dilek; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüNew flurbiprofen derivatives containing 1,2,4-triazoline-5-thione (4) and thioethers (5a-r) were synthesized in this study. The structures of synthesized compounds were characterized by spectral methods (FT-IR, 1H NMR, 13C NMR) and 19F NMR (only compound 5l), besides elemental analysis. In addition, molecular binding of these compounds to the human methionine aminopeptidase 2 enzyme was performed using AutoDock 4.2, the software product of the research, computationally. All synthesized compounds were evaluated for cytotoxic effect against MDA-MB231 triple-negative breast cancer cell line by using WST-1 Cell Viability and Proliferation assay. Doxorubicin is in the anthracycline class and is an antineoplastic agent. It is used to provide regression in common neoplastic conditions such as breast carcinoma. Due to the cardiovascular side effects of doxorubicin, a combination study was conducted with the (& PLUSMN;)(R,S)-3-{1-[2-fluoro-(1,1 & PRIME;-biphenyl)-4-yl]ethyl}-4-methyl-5-{[2(trifluoromethyl)benzyl]thio}-4H-1,2,4-triazole (5l) with promising cytotoxic effects. As a result of the combination, it was shown as 7% MDA-MB231 cell viability. Therefore, based on the evaluations, a better cytotoxic effect was achieved with the 5l combination depending on the low dose of doxorubicin.Article Citation Count: 0Synthesis and Evaluation of Novel Metacetamol Derivatives With Hydrazone Moiety as Anticancer and Antimicrobial Agents(Wiley-v C H verlag Gmbh, 2023) Küçükgüzel, Şükriye Güniz; Atlihan, Irem; Cayir, Elif; Tiber, Pinar Mega; Orun, Oya; Nigiz, Seyma; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüBy exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, H-1 and C-13-NMR, and mass spectroscopic methods. The obtained molecules (3 a-j) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazinyl)-2-oxoethoxy)phenyl)acetamide (3 e) was found to be the most effective derivative with an IC50 value of 9.89 & mu;M against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3 e in the colchicine binding pocket of tubulin. Additionally, compound 3 e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC=8 & mu;g/ml), indicating that nitro group at the 4(th) position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3 e could be exploited as a leading structure for further anticancer and antifungal drug development.Article Citation Count: 9Synthesis and Biological Evaluation of Novel Aryloxyacetic Acid Hydrazide Derivatives as Anticancer Agents(Taylor & Francis inc, 2021) Küçükgüzel, Şükriye Güniz; Erdogan, Omer; Cevik, Ozge; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüIn 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.Article Citation Count: 13Design, Synthesis and Anticancer Activity Studies of Novel 4-Butylaminophenyl Hydrazide-Hydrazones as Apoptotic Inducers(Pergamon-elsevier Science Ltd, 2022) Küçükgüzel, Şükriye Güniz; Baysal, Ozge Deniz Yesil; Basaran, Guzide Satir; Sezer, Gulay; Telci, Dilek; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüIn this study, a series of the novel Tetracaine derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (H-1-C-13 NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds (2a-1) were screened for anticancer activity against human hepatocellular carcinoma (HepG2) and lung carcinoma (A549) cell lines. Against HepG2 and A549 cell lines, among the synthesized compounds, 4-(Butylamino)-N'-[(2,4-dichlorophenyl)methylidene]benzohydrazide (2i) demonstrated the most potent anticancer activity with IC50 values 28 and 7 mu M, respectively. Possible cytotoxic effects of compounds (2a-1) on both normal human lung fibroblast (MCR-5) and normal human dermal fibroblast (HDF) cell lines were assessed. Inhibition of anti-apoptotic protein Bax and Bcl-2 was investigated in HepG2 and A549 cells treated with compound 2i using qRT-PCR. Apoptosis was also detected by Annexin V studies. The flow cytometric analysis results showed that compound 2i treatment of HepG2 and A549 cells significantly increased apoptotic cell populations while decreasing viabilities in these carcinomas in a dose-dependent manner after 72 h of incubation. (C) 2022 Elsevier Ltd. All rights reserved.
