- Synthesis and biological activities of diflunisal hydrazide-hydrazones
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Several diflunisal hydrazide-hydrazone derivatives namely 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [(5-nitro-2-furyl/substitutedphenyl)methylene] hydrazide (3a-o) have been synthesised. Methyl 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylate (1) a
- Kuecuekguezel, S. Gueniz,Mazi, Adil,Sahin, Fikrettin,Oeztuerk, Suzan,Stables, James
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- Synthesis, molecular docking and anticancer activity of diflunisal derivatives as cyclooxygenase enzyme inhibitors
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Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation, the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings, we have synthesized some new diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against androgen-independent prostate adenocarcinoma (PC-3), colon carcinoma (HCT-116), human breast cancer (T47D), breast carcinoma (MCF7) and human embryonic kidney (HEK-293) cell lines. Specifically, the diflunisal and thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the breast cancer cell line T47D, whereas compounds 6 and 10 which are thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116 cancer cell line with the tested thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the diflunisal and thiosemicarbazide functionalities potentiate anticancer activity on prostate cancer and the thiosemicarbazide functionality decreases the anticancer activity of diflunisal on colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2 enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2 isozyme over COX-1, which is in agreement with the experimental results.
- Co?kun, G?knil Pelin,Djikic, Teodora,Hayal, Taha Bartu,Türkel, Nezaket,Yelek?i, Kemal,?ahin, Fikrettin,Kü?ükgüzel, ?. Güniz
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- Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors
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Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. We have previously identifi
- Senkardes, Sevil,Kaushik-Basu, Neerja,Durmaz, Irem,Manvar, Dinesh,Basu, Amartya,Atalay, Rengul,Guniz Kucukguzel
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- Synthesis of 1-aroyl-3,5-dimethyl-1H-pyrazoles as anti-HCV and anticancer agents
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1-Aroyl-3,5-dimethyl-1H-pyrazole derivatives (7-12) were synthesized from some hydrazides (1-6) with acetylacetone (2,4-pentanedione) by microwave irradiation. Their structures were elucidated by FT-IR and 1H-NMR spectral data and elemental analysis. Compound activities were evaluated against HCV NS5B and in cell based HCV reporters. Compound 8 was the most promising of this series in inhibiting intracellular NS5B activity and HCV RNA replication in reporter cells. The selected compounds 9, 10 and 12 by National Institue of Health were screened for their anticancer activity against 60 human tumor cell lines. Compound 9 (3-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-2′,4′- difluorobiphenyl-4-ol) possessed significant activity against human immortalized myelogenous leukemia (K-562) exhibiting cell growth promotion 30.05%, with inhibition of 69.95% at 10-5M concentration. Compounds 3 and 9 were evaluated for cell viability and growth inhibition by K-562 cells of MTT assay, at different doses (10-6- 10-2M). Further, compound 9 exhibited anticancer activity against K-562 cells with IC50 value of 4 μM . Apoptosis levels of compound 9 were determined for three different concentrations (10-6, 10-5 and 10-3M) at two time points (24 and 48 h). Compound 9 induced apoptosis of K-562 cells, thus suggesting that compound 9 might be a potential chemopreventive agent for chronic myelogenous leukemia.
- Aydin, Sevil,Kaushik-Basu, Neerja,Oezbas-Turan, Suna,Akbuga, Juelide,Tiber, Pinar Mega,Orun, Oya,Gurukumar,Basu, Amartya,Kuecuekguezel, S. Gueniz
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p. 121 - 131
(2014/03/21)
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- Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents
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Three novel series of 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylic acid derivatives namely 4-substituted-1,2,4-triazoline-3-thiones (4a-g); 2-substituted-1,3,4-thiadiazoles (5a-g) and 2-substituted-1,3,4-oxadiazoles (6a-g) have been synthesized. Twenty-o
- Kuecuekguezel, S. Gueniz,Kuecuekguezel, Ilkay,Tatar, Esra,Rollas, Sevim,Sahin, Fikrettin,Guelluece, Medine,De Clercq, Erik,Kabasakal, Levent
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p. 893 - 901
(2008/03/17)
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