Küçükgüzel, İlkay
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Kucukguzel, Ilkay
Kucukguzel, Ilkay
Küçükgüzel, İ.
Küçükgüzel, İlkay
Kucukguzel, Ilkay
Küçükgüzel, İ.
Küçükgüzel, İlkay
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ilkay.kucukguzel@fbu.edu.tr
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Eczacılık Meslek Bilimleri Bölümü
Eczacılık Meslek Bilimleri Bölümü
Eczacılık Meslek Bilimleri Bölümü
Eczacılık Meslek Bilimleri Bölümü
Eczacılık Meslek Bilimleri Bölümü
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3
GOOD HEALTH AND WELL-BEING
9
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11
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11
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4
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0
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Now showing 1 - 10 of 11
Article Citation - WoS: 1Citation - Scopus: 1Novel Triazole-Urea Hybrids as Promising EGFR Inhibitors: Synthesis, Molecular Modeling and Antiproliferative Activity Studies Against Breast Cancer(Elsevier, 2025) Ture, Asli; Gulcan, Mehmet Metehan; Birgul, Serap Ipek Dingis; Erdogan, Oguz; Erdogan, Omer; Tuncay, Fulya Oz; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri BölümüBreast cancer is the second leading cause of mortality among women globally. In this study, novel promising urea derivatives containing a 4-phenyl-5-sulphanylidene-4,5-dihydro-1H-1,2,4-triazole group were synthesized and evaluated for their biological activities against breast cancer. The cytotoxicity and apoptotic profiles of these compounds were assessed on the MCF7 breast cancer cell line and the L929 fibroblast cell line. Compound 5c exhibited the strongest anticancer activity against MCF7 cells with an IC50 value of 56.97+4.22 mu M, while it showed significantly lower cytotoxicity against L929 cells (IC50 = 1651+18.39 mu M). Compound 5c also induced early apoptosis in MCF7 cells, with an apoptosis rate of 18.40% and 5.28%, respectively. Additionally, the EGFR inhibitory activities of the synthesized compounds were evaluated, with compound 5i demonstrating the most potent EGFR inhibition, showing an IC50 value of 35.1 nM. These results suggest that compound 5c likely exerts its anticancer effects through mechanisms other than EGFR inhibition, while compound 5i has significant potential as an effective EGFR inhibitor. Molecular modeling studies were conducted to suggest putative binding interactions of compounds 5d, 5e and 5i with wildtype hEGFR. Further studies are warranted to explore their activity against other cancer types.Article Citation - Scopus: 1Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates(2023) Kulabaş, Necla; Gurboga, Merve; Özakpınar, Özlem Bingöl; Liu, Jianyang; Jakobson, Per-johan; Danış, Özkan; Küçükgüzel, İlkay; Eczacılık Meslek Bilimleri BölümüBaşlangıç maddesi olarak parasetamol kullanılarak bazı yeni triazol içeren asetamid türevleri 9-20 sentezlendi ve yapıları FTIR, NMR (1H and 13C) ve kütle spektral verileri ile karakterize edildi. Beş insan kanser hücre hattına (akciğer kanseri A549, kronik miyelojenöz lösemi K562, meme kanseri MCF-7, prostat kanseri PC-3, nöroblastoma SH-SY5Y hücre hatları) karşı sentezlenen tüm moleküllerin in vitro sitotoksik aktiviteleri incelendi ve ayrıca seçiciliği tanımlamak için fare embriyonik fibroblast hücreleri (NIH/3T3) üzerinde sitotoksik etkileri MTT yöntemiyle test edildi. Ek olarak, on iki hedef bileşik 9-20, mPGES-1 ve COX-1/2 inhibe edici etkileri açısından tarandı. Sentezlenen bileşiklerin hiçbiri hem kanser hücrelerine hem de mPGES-1 ve COX-1/2 enzimlerine karşı anlamlı bir inhibisyon göstermezken, sağlıklı hücrelere karşı da sitotoksik olmadıkları belirlendi. Son olarak yeni sentezlenen bileşiklerin ADMET özellikleri in siliko yöntemler kullanılarak tahmin edildi.Article Citation - WoS: 3Citation - Scopus: 3Synthesis of Novel Triazole-Urea Hybrids and Their Antiproliferative Activity Against Pancreatic Cancer Through Suppression of Eef2k and Induction of Apoptosis(Elsevier, 2024) Tuere, Asli; Ozdemir, Burcu; Cece, Onur; Armagan, Guliz; Erdogan, Mumin Alper; Erdogan, Omer; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri BölümüPancreatic cancer is one of the deadliest cancers with its highly aggressive and metastatic character and there is a huge unmet need for new drugs treating pancreatic cancer. In the present study, a series of 1,2,4-triazole-urea conjugates have been designed and synthesized as novel candidates of antiproliferative agents against pancreatic cancer cells. Among them, compounds 33, 34, 35 and 38 possesing IC50 values between 0.231 and 0.488 mu M against PANC-1 cells demonstrated the highest anti-proliferative activity. These compounds presenting the highest antiproliferative activity were evaluated for further biological studies. The same four compounds inhibited colony formation in pancreatic cancer cells dose dependently. Western blot study on the selected compounds showed that compounds 33 and 38 significantly reduced eEF2K protein levels in cancer cells. These compounds displayed an effective eEF2K activity suppression by down-regulated levels of unphosphorylated eEF2 in PANC-1 cells. Compounds 33, 34, 35 and 38 were also demonstrated to induce apoptosis and activate caspase 3/7. In silico studies were performed to predict the druggability and ADMET/ properties of the active molecules. In summary, 1,2,4-triazole-urea conjugates developed in this study represent a novel and promising lead structure with anticancer activity against pancreatic cancer achieved through eEF2K activity suppression. Compounds being referred to are the first "triazole-urea hybrid" molecules found to be effective against pancreatic cancer.Article Bangladesh Journal of Pharmacology(Bangladesh Pharmacological Soc, 2024) Kulabas, Necla; Guven, Cansu Tamniku; Duracik, Merve; Ozakpinar, Ozlem Bingol; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri Bölümü[No Abstract Available]Article Synthesis, Molecular Modeling, Anti-Cancer and COX-1/2 Inhibitory Activities of Novel Thiazolidinones Containing Benzothiazole Core(Bangladesh Pharmacological Soc, 2025) Kulabas, Necla; Guven, Cansu Tamniku; Duracik, Merve; Ozakpinar, Ozlem Bingol; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri BölümüIn this study, new 1,3-thiazolidin-4-one derivatives containing arylmethylene groups in the 5-position were obtained from 6-(trifluoromethoxy)-1,3-benzo-thiazol-2-amine (riluzole). Synthesized compounds were characterized by spectral data and elemental analysis. In vitro, cytotoxic activities of the synthesized molecules were evaluated against the human lung cancer (A549) and human prostate cancer (PC-3) cell lines. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Ten target compounds 3-12 were also screened for their COX-1 and COX-2 inhibitory activities. Of these compounds, 4 showed the highest COX-2 inhibition at 10 mu M. Molecular docking calculations were performed to understand the binding interactions of compounds with COX-1 and COX-2 proteins. In silico studies of the tested compounds represented important binding modes that may be responsible for their anti-cancer activity via selective inhibition of the COX-2 enzyme. ADMET predictions were conducted to assess the drug-like properties of the novel compounds.Article In Silico Evaluation of H1-Antihistamine as Potential Inhibitors of SARS-CoV RNA-Dependent RNA Polymerase: Repurposing Study of COVID-19 Therapy(Turkish Pharmacists Association, 2024) Küçükgüzel, İlkay; Kulabaş, Necla; Hamdan, Mazın; Eczacılık Meslek Bilimleri BölümüIntroduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), from the family Coronaviridae, is the seventh known coronavirus to infect humans and cause acute respiratory syndrome. Although vaccination efforts have been conducted against this virus, which emerged in Wuhan, China, in December 2019 and has spread rapidly around the world, the lack of an Food and Drug Administration-approved antiviral agent has made drug repurposing an important approach for emergency response during the COVID-19 pandemic. The aim of this study was to investigate the potential of H1-antihistamines as antiviral agents against SARS-CoV-2 RNA-dependent RNA polymerase enzyme. Materials and Methods: Using molecular docking techniques, we explored the interactions between H1-antihistamines and RNA-dependent RNA polymerase (RdRp), a key enzyme involved in viral replication. The three-dimensional structure of 37 H1-antihistamine molecules was drawn and their energies were minimized using Spartan 0.4. Subsequently, we conducted a docking study with Autodock Vina to assess the binding affinity of these molecules to the target site. The docking scores and conformations were then visualized using Discovery Studio. Results: The results examined showed that the docking scores of the H1-antihistamines were between 5.0 and 8.3 kcal/mol. These findings suggested that among all the analyzed drugs, bilastine, fexofenadine, montelukast, zafirlukast, mizolastine, and rupatadine might bind with the best binding energy (< -7.0 kcal/mol) and inhibit RdRp, potentially halting the replication of the virus. Conclusion: This study highlights the potential of H1-antihistamines in combating COVID-19 and underscores the value of computational approaches in rapid drug discovery and repurposing efforts. Finally, experimental studies are required to measure the potency of H1-antihistamines before their clinical use against COVID-19 as RdRp inhibitors.Article Synthesis of Novel Thiazole/Thiadiazole Conjugates of Fluoroquinolones as Potent Antibacterial and Antimycobacterial Agents(John Wiley and Sons Inc, 2025) Poyraz Yılmaz, P.; Kulabaş, N.; Bozdeveci, A.; Vagolu, S.K.; Imran, M.; Tatar, E.; Küçükgüzel, İ.; Eczacılık Meslek Bilimleri BölümüTwenty azole-fluoroquinolone hybrids were designed and synthesized by conjugating thiazole and thiadiazole structures to ciprofloxacin and norfloxacin via a 2-oxoethyl bridge. The structures and purities of the synthesized compounds were proven by spectral techniques. The antimycobacterial effects of target compounds 21–40 were tested against Mycobacterium tuberculosis H37Rv strain. Among the 20 synthesized compounds, 12 exhibited minimal inhibition concentration (MIC) values in the range of 1.56–25 μg/mL. Among the molecules screened for antimycobacterial effects, the most effective was compound 35, a thiadiazole-ciprofloxacin hybrid. The cytotoxic effect of this molecule was found to be lower than the reference drugs, and it was also determined to be a more effective inhibitor than ciprofloxacin and norfloxacin in the DNA-gyrase supercoiling test. The antimicrobial effects of compounds 21–40 were screened by agar-well diffusion and microdilution tests against Gram-positive/negative bacteria, a fast-growing mycobacterium, and two yeast strains. While most of the compounds tested showed antibacterial effects, the most effective fluoroquinolone derivative appeared to be compound 31 with an MIC value of < 0.63 μg/mL against all Gram-negative bacteria tested. Azole-fluoroquinolone hybrids 21–40 did not show any activity against non-pathogenic Lactobacillus species and yeast-like fungi, indicating that they have selective antibacterial and antimycobacterial activity, particularly against Gram-negative bacteria. In silico molecular docking studies were conducted to uncover the interactions between lead compound 35 and the DNA gyrase proteins of M. tuberculosis and S. aureus. Additionally, a 100 ns molecular dynamics simulation was carried out to assess the stability of the complexes formed between compound 35 and both proteins. © 2025 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.Article Citation - Scopus: 1Synthesis and Anti-Hcv Activity of Novel 5-Arylmethylene Derivatives Via Suppression of Ns5b Polymerase and Cox-2(Elsevier, 2024) Kulabas, Necla; Lee, Jin-Ching; Ozakpinar, Ozlem Bingol; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri BölümüHepatitis C (HCV) is a viral infection that leads to forms of acute and chronic liver disease, including cirrhosis (scarring of the liver) and liver cancer. The World Health Organization (WHO) estimated in 2019 that approximately 290,000 people died from hepatitis C (mostly from cirrhosis and hepatocellular carcinoma). Directacting antiviral drugs (DAAs) can cure more than 95% of individuals with hepatitis C infection, while research on the discovery of new antiviral agents is still ongoing. The Hepatitis C virus (HCV) can cause various biochemical changes in liver cells, and some of these changes are associated with the COX-2 enzyme. The identification of its role in promoting growth in liver cells as well as its involvement in various cancer types, including hepatocellular carcinoma, has made COX-2 an important target in the development of new agents effective against HCV. In this study, thirty-six new 5-arylmethylene-2-imino-1,3-thiazolidin-4-one derivatives (5a-s, 6a-s) were synthesized through Knoevenagel condensation of 2-[(4-substitutedpyridin-2-yl)imino]-1,3thiazolidin-4-one derivatives with various aldehydes. Structures of the synthesized compounds were elucidated by the use of spectral and chromatographic techniques, besides elemental analyses. Four compounds were selected for further studies as they were found to suppress the NS5B protein with anti-HCV activity using the Western Blotting method. The selected compounds 5o, 6m, 6r, and 6s inhibited HCV with EC50 values of 8.0 +/- 0.2 mu M, 13.9 +/- 0.45, 9.2 +/- 0.2 mu M, and 12.1 +/- 0.1 mu M, respectively. It was determined that these compounds reduced HCV-induced COX-2 promoter activity in Ava5 cells compared to Huh7 cells. The antiviral effects of the compounds were also investigated on DENV, closely related to HCV due to sharing certain biological, structural, and mechanical properties throughout their life cycles. However, no significant effect was observed in the preliminary screening study, indicating the compounds' specificity for HCV. Considering the relationship between HCV, DENV, and COX-2, the compounds' COX-1 and COX-2 enzyme inhibition potentials were investigated both in vitro and in silico. Compounds 6d, 6e, 6f, and 6m, which exhibited high selective COX-2 inhibition, were discussed for their interactions with the active site. Our study revealed that our target compounds suppressed COX-2 both at the protein level and through enzyme inhibition, thus providing promising findings for the discovery of new anti-HCV effective COX-2 inhibitors.Article Citation - WoS: 5Citation - Scopus: 6in Silico Design, Synthesis and Antitubercular Activity of Novel 2-Acylhydrazono as Enoyl-Acyl Carrier Protein Reductase Inhibitors(Taylor & Francis inc, 2024) Birgul, Serap Ipek Dingis; Kumari, Jyothi; Tamhaev, Rasoul; Mourey, Lionel; Lherbet, Christian; Sriram, Dharmarajan; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri BölümüMycobacteria regulate the synthesis of mycolic acid through the fatty acid synthase system type 1 (FAS I) and the fatty acid synthase system type-2 (FAS-II). Because mammalian cells exclusively utilize the FAS-I enzyme system for fatty acid production, targeting the FAS-II enzyme system could serve as a specific approach for developing selective antimycobacterial drugs. Enoyl-acyl carrier protein reductase enzyme (MtInhA), part of the FAS-II enzyme system, contains the NADH cofactor in its active site and reduces the intermediate. Molecular docking studies were performed on an in-house database (similar to 2200 compounds). For this study, five different crystal structures of MtInhA (PDB Code: 4TZK, 4BQP, 4D0S, 4BGE, 4BII) were used due to rotamer difference, mutation and the presence of cofactors. Molecular dynamics simulations (250 ns) were performed for the novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones derivatives selected by molecular docking studies. Twenty-three compounds selected by in silico methods were synthesized. Antitubercular activity and MtInhA enzyme inhibition studies were performed for compounds whose structures were elucidated by IR,H-1-NMR,C-13-NMR, HSQC, HMBC, MS and elemental analysis. Communicated by Ramaswamy H. SarmaArticle Synthesis, Molecular Modeling, Anti-Cancer and COX-1/2 Inhibitory Activities of Novel Thiazolidinones Containing Benzothiazole Core(Bangladesh Pharmacological Society, 2024) Kulabas, Necla; Guven, Cansu Tamniku; Duracık, Merve; Bingol Ozakpinar, Ozlem; Küçükgüzel, İlkay; Eczacılık Meslek Bilimleri BölümüIn this study, new 1,3-thiazolidin-4-one derivatives containing arylmethylene groups in the 5-position were obtained from 6-(trifluoromethoxy)-1,3-benzo-thiazol-2-amine (riluzole). Synthesized compounds were characterized by spectral data and elemental analysis. In vitro, cytotoxic activities of the synthesized molecules were evaluated against the human lung cancer (A549) and human prostate cancer (PC-3) cell lines. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Ten target compounds 3-12 were also screened for their COX-1 and COX-2 inhibitory activities. Of these compounds, 4 showed the highest COX-2 inhibition at 10 μM. Molecular docking calculations were performed to understand the binding interactions of compounds with COX-1 and COX-2 proteins. In silico studies of the tested compounds represented important binding modes that may be responsible for their anti-cancer activity via selective inhibition of the COX-2 enzyme. ADMET predictions were conducted to assess the drug-like properties of the novel compounds. © 2024 Elsevier B.V., All rights reserved.
