Browsing by Author "Kurnaz, Isil Aksan"

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4H-Pyran-4-one derivatives:
(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2009-01-01) Us, Demet; Gurdal, Ece; Berk, Barkin; Oktem, Sinem; Kocagoz, Tanil; Caglayan, Berrak; Kurnaz, Isil Aksan; Erol, Dilek Demir
A series of 3-hydroxy-6-methyl-2-((4-substitutedpiperazin-1-yl)methyl)-4H-pyran-4-on e structured compounds were synthesized by reacting 5-hydroxy-2-methyl-4H-pyran-4-one with suitable piperazine derivatives using Mannich reaction conditions. Antibacterial activities of the compounds for E. coli, S. paratyphi, S. flexneri, E. gergoviae, and M. smegmatis were assessed in vitro by using broth dilution for determination of the minimum inhibitory concentration (MIC). In addition, their inhibitory effects over DNA gyrase enzyme were evaluated using a DNA gyrase supercoiling assay. Among the synthesized compounds
In silico analyses and global transcriptional profiling reveal novel putative targets for Pea3 transcription factor related to its function in neurons
(PUBLIC LIBRARY SCIENCE, 2017-01-01) Kandemir, Basak; Dag, Ugur; Gungor, Burcu Bakir; Durasi, Ilknur Melis; Erdogan, Burcu; Sahin, Eray; Sezerman, Ugur; Kurnaz, Isil Aksan
Pea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells. We not only show that quite a number of genes in cancer, immune system and cell cycle pathways, among many others, are either up- or down-regulated by Pea3, but also identify novel targets including ephrins and ephrin receptors, semaphorins, cell adhesion molecules, as well as metalloproteases such as kallikreins, to be among potential target promoters in neuronal systems. Our overall results indicate that rather than early stages of neurite extension and axonal guidance, Pea3 is more involved in target identification and synaptic maturation.
Mannich base derivatives of 3-hydroxy-6-methyl-4H-pyran-4-one with antimicrobial activity
(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2010-01-01) Us, Demet; Berk, Barkin; Gurdal, Ece; Aytekin, Nihan; Kocagoz, Tanil; Caglayan, Berrak; Kurnaz, Isil Aksan; Erol, Dilek Demir
A series of 3-hydroxy-6-methyl-2-{[}(substitutedpiperidine-1-yl)methyl]-4H-pyran-4-o ne structured compounds were synthesized by reacting 5-hydroxy-2-methyl-4H-pyran-4-one with suitable piperidine derivatives using Mannich reaction conditions. Antibacterial activities of the compounds for E. coli ATCC 25922, S. paratyphi ATCC BAA-1250, S. flexneri ATCC 12022, E. gergoviae ATCC 33426, and M. smegmatis ATCC 14468 were assessed in vitro by the broth dilution method for determination of minimum inhibitory concentration (MIC). In addition, their inhibitory effects over DNA gyrase enzyme were evaluated using a DNA gyrase supercoiling assay. All the synthesized compounds showed a MIC value of either 8 or 16 mu g/mL for M. smegmatis, whereas minimum to moderate activity was achieved for the others. Those tested in the supercoiling assay had at best a very mild inhibition of the enzyme. This series deserves further attention for testing over Mycobacterium species and topoisomerase II inhibition to develop new lead drugs to treat non-tuberculous mycobacterial infections.
Molecular modeling and antimycobacterial studies of Mannich bases: 5-hydroxy-2-methyl-4H-pyran-4-ones
(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2011-01-01) Berk, Barkin; Us, Demet; Oktem, Sinem; Kocagoz, Z. Tanil; Caglayan, Berrak; Kurnaz, Isil Aksan; Erol, Dilek Demir
The World Health Organization lists tuberculosis among the top 3 leading causes of death from a single infectious agent, and reported cases of multidrug-resistant tuberculosis (MDR-TB) are on the rise. In an attempt to improve MDR-TB drug-directed therapy, we synthesized 11 4-substituted piperazine derivatives of 3-hydroxy-6-methyl-4H-pyran-4-one pharmacophore by reacting 5-hydroxy-2-methyl-4H-pyran-4-one with suitable piperazine derivatives under Mannich reaction conditions. Inhibitory effects of the 11 compounds on Escherichia coli DNA gyrase were evaluated via DNA gyrase supercoiling assay. The minimum inhibitory concentrations (MIC) of the 11 compounds and 41 compounds from our previous studies against Mycobacterium tuberculosis H37RV were assessed, in vitro, by a broth dilution method. To determine the interaction pattern between active site amino acids and all 52 compounds, homology modeling for the construction of M. tuberculosis DNA gyrase B subunit was performed, followed by a docking study. The data presented here could prove useful in future studies on interaction field analysis and high throughput virtual screening of the derivatives of the 3-hydroxy-6-methyl-4H-pyran-4-one pharmacophore toward the development of more clinically applicable compounds.