Browsing by Author "Caglayan, Berrak"

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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
Interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival
(NATURE PUBLISHING GROUP, 2019-01-01) Beker, Mustafa C.; Caglayan, Berrak; Caglayan, Ahmet B.; Kelestemur, Taha; Yalcin, Esra; Caglayan, Aysun; Kilic, Ulkan; Baykal, Ahmet T.; Reiter, Russel J.; Kilic, Ertugrul
The circadian rhythm is driven by a master clock within the suprachiasmatic nucleus which regulates the rhythmic secretion of melatonin. Bmal1 coordinates the rhythmic expression of transcriptome and regulates biological activities, involved in cell metabolism and aging. However, the role of Bmal1 in cellular- survival, signaling, its interaction with intracellular proteins, and how melatonin regulates its expression is largely unclear. Here we observed that melatonin increases the expression of Bmal1 and both melatonin and Bmal1 increase cellular survival after oxygen glucose deprivation (OGD) while the inhibition of Bmal1 resulted in the decreased cellular survival without affecting neuroprotective effects of melatonin. By using a planar surface immunoassay for PI3K/AKT signaling pathway components, we revealed that both melatonin and Bmal1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3 alpha beta, and p70S6K. In contrast, inhibition of Bmal1 resulted in decreased phosphorylation of these proteins, which the effect of melatonin on these signaling molecules was not affected by the absence of Bmal1 . Besides, the inhibition of PI3K/AKT decreased Bmal1 expression and the effect of melatonin on Bmal1 after both OGD in vitro and focal cerebral ischemia in vivo. Our data demonstrate that melatonin controls the expression of Bmal1 via PI3K/AKT signaling, and Bmal1 plays critical roles in cellular survival via activation of survival kinases.
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.