Browsing by Author "Erdogan, Omer"

Now showing 1 - 5 of 5

Citation Count: 6
Design, 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 Bölümü
In 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.
Citation Count: 3
Novel Azole-Urea Hybrids as Vegfr-2 Inhibitors: Synthesis, In Vitro Antiproliferative Evaluation And In Silico Studies
(Elsevier, 2023) Küçükgüzel, İlkay; Kulabas, Necla; Erdogan, Omer; Cevik, Ozge; Dere, Damla; Yelekci, Kemal; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri Bölümü
The vascular endothelial growth factor receptor-2 (VEGFR-2) is a receptor tyrosine kinase known to be abnormally expressed in various malignant tumors, including breast cancer, and is considered one of the most important contributors to tumor angiogenesis. Sorafenib is one of many VEGFR-2 inhibitors that have received approval for clinical use from the US FDA in recent years. Accordingly, in this study, the synthesis of two new pyrazoles, six 1,3,4-oxadiazoles, four 1,3,4-thiadiazoles, and ten 1,2,4-triazole-3-thione derivatives having structural characteristics similar to sorafenib was carried out. A preliminary screening of synthesized compounds and known inhibitors sorafenib and staurosporine at 10 mu M concentration on in vitro activity of VEGFR-2 was performed, and compounds 10c, 8a, and 11 g were identified as the most potent derivatives with% VEGFR-2 residual activities lower than 30%, and dose-dependent inhibition studies was carried out to determine the IC50 values of these inhibitors. Compound 10c was found to be the most potent inhibitor of VEGFR-2 activity with an IC50 value of 0.664 mu M. The anti-proliferative activity of synthesized derivatives was assessed against a breast carcinoma (MCF-7) cell line, a triple negative human breast adenocarcinoma (MDA-MB-231) cell line, and noncancerous fibroblast cells (L929). Compound 8a displayed superior activity when compared to sorafenib against MCF-7 (7.69 fold) and MDA-MB-231 (1.52 fold) cell lines while displaying 3.75-fold less toxicity against the normal L929 cell line. Annexin V binding assay revealed that compound 8a significantly increased early and late apoptosis in MCF-7 cells and late apoptosis and necrosis in MDA-MB-231 cells. Computational studies such as molecular docking and ADMET evaluation were performed to elucidate the binding interactions and druglikeness of the synthesized compounds. The results indicate that compound 8a could be a promising candidate for the development of a novel anti-angiogenic and anti-proliferative agent.
Citation Count: 0
The Protective Effects Of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats
(Galenos Publ House, 2022) Ede Pazarbaşı, Seren; Şener, Göksel; Cevik, Ozge; Erdogan, Omer; Kaya, Ozlem Tugce Cilingir; Ede, Seren; Sener, Goksel; Eczane Hizmetleri Bölümü; Eczacılık Meslek Bilimleri Bölümü
BACKGROUND/AIMS: Methotrexate (MTX), a cytotoxic therapeutic agent, is used for the cure of malignancies and rheumatologic disorders. However, the significant side effects of MTX limits its use. In this study, we aim to assess the hepatoprotective properties of Momordica charantia (MC) against MTX-induced liver damaged in rats.MATERIALS AND METHODS: Following one dose of MTX (20 mg/kg), the rats were given either distilled water or MC extract (300 mg/kg, po) for 5 days. After the dissection of the rats, the liver was removed to analyse tumour necrosis factor -a (TNF-a), interleukin-113 (IL-113), transforming growth factor 13 (TGF-13) and 8-hydroxy-2'-deoxy-guanosine (8-OhdG) levels and superoxide dismutase (SOD), catalase (CAT), and caspase-3 activities. The tissues were also examined histopathologically.RESULTS: The hepatic TNF-a, IL-113, TGF-13, 8-OhdG levels, and Caspase-3 activity in the MTX group were found to be significantly increased compared to the control group. However, MC extract was able to significantly decrease TNF-a, TGF-13, 8-OhdG levels, and Caspase-3 activity. Also, both the SOD and CAT activity of the MTX group decreased compared to the control group. Although only the SOD levels elevated significantly with MC treatment, the SOD and CAT activities of the MC treated group were similar to the control group. Supporting these biochemical parameters, MTX-induced histologic alterations in the liver were also ameliorated via MC treatment.CONCLUSION: Our results demonstrated that MC has a protective role against MTX-induced hepatic tissue injury by reducing apoptosis, oxidative damage, and the expression of pro-inflammatory cytokines.
Citation Count: 9
Synthesis 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 Bölümü
In 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.
Citation Count: 0
Synthesis of Novel Triazole-Urea Hybrids and Their Antiproliferative Activity Against Pancreatic Cancer Through Suppression of Eef2k and Induction of Apoptosis
(Elsevier, 2024) Küçükgüzel, İlkay; Ozdemir, Burcu; Cece, Onur; Armagan, Guliz; Erdogan, Mumin Alper; Erdogan, Omer; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri Bölümü
Pancreatic 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.