Yıldızeli Meslek Yüksekokulu Makale Koleksiyonu
https://hdl.handle.net/20.500.12418/728
2024-03-29T11:05:26ZEffect of azomethine group containing compounds on gene profiles in Wnt and MAPK signal patterns in lung cancer cell line: In silico and in vitro analyses
https://hdl.handle.net/20.500.12418/14871
Effect of azomethine group containing compounds on gene profiles in Wnt and MAPK signal patterns in lung cancer cell line: In silico and in vitro analyses
Agbektas, Tugba; Zontul, Cemile; Ozturk, Alpaslan; Huseynzada, Alakbar; Ganbarova, Rana; Hasanova, Ulviyya; Cinar, Gulcihan; Tas, Ayca; Kaya, Savas; Chtita, Samir; Silig, Yavuz
The main aims of anticancer drug development studies is to reduce the toxicity of the developed compound and maximize the effectiveness, as well as the discovery of artificial and natural compounds. In recent years, scientists have accelerated their research on new molecules with anticancer activity. In recent years, new drugs containing the azomethine group are thought to be promising in the treatment of cancer. In this study, firstly, the synthesis of azomethine group-containing compounds, i.e. Schiff bases, which was designed theoretically, was carried out. Secondly, the application of the newly synthesized compounds 1, 2, 3 and 4 to the lung cancer cell line (A-549), followed by the determination of their anticancer activities, and finally the Wnt signaling pathway (CSNK1A1, CTNNB1), MAPK signaling pathway (DUSP1, DUSP2, DUSP4 and DUSP10) genes on expression levels was investigated. The compounds synthesized in our study were characterized by 1H and 13C NMR spectroscopy methods. The anticancer activities of the new synthesized molecules were determined in the A-549 lung cancer cell line using the MTT method. Expression levels of Wnt signaling pathway (CSNK1A1, CTNNB1) and MAPK signaling pathway (DUSP1, DUSP2, DUSP4 and DUSP10) genes were determined by RT-PCR method. In addition, A-549 cells were evaluated in terms of biochemical parameters. In addition to experimental studies, theoretical studies were carried out. Molecular docking results were found to be compatible with the experiments. Compounds 1, 2, 3 and 4 applied to cell line A-549 showed the highest activity after 72 h of incubation. As a result, it was determined that compounds 2 and 4 increased the expression of CTNNB1 and DUSP10 genes compared to the control group. It was determined that compound 4 increased the expression level of CSNK1A1, CTNNB1, DUSP1, DUSP2, DUSP4 and DUSP10 genes compared to other groups. A-549 lung cancer cells showed a 70% reduction in GST levels in compound 1, while a 96% reduction in CAT levels in compound 1 compared to the control group. Molecular docking calculations supported the Experimental observations. Calculated binding energies provided important clues about drug efficiencies of molecules studied.
0005-01-01T00:00:00ZAnticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
https://hdl.handle.net/20.500.12418/14858
Anticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
Inandiklioglu, Nihal; Tas, Ayca; Agbektas, Tugba; Tuncbilek, Zuhal; Raheem, Kayode Yomi; Cinar, Gulcihan; Silig, Yavuz
Neuroblastoma is the most common extracranial solid tumor of infancy in a broad range of clinical courses, ranging from spontaneous regression to fatal progression. Telomere maintenance plays an impor- tant role in genome stability and cell proliferation. Telomerase reverse transcriptase (hTERT in humans) is a catalytic subunit of the enzyme telomerase. In this study, it was aimed to determine the anticancer ac- tivity of the docetaxel chemotherapeutic agent in neuroblastoma cell line (SH-SY5Y) and to investigate its effect on hTERT gene expression level and telomere length. Molecular docking studies were performed on docetaxel with the crystal structure of telomerase. The electronic properties of docetaxel were calculated using the density functional theory (DFT) method. SH-SY5Y cells were treated for 24, 48 and 72 h with specific concentrations of docetaxel drug ranging from 1 to 100 μg/ml. IC50 doses of docetaxel were de- termined and administered to SH-SY5Y cells, followed by RNA isolation. hTERT and MYC gene expression levels and telomere length were measured in the docetaxel-treated sample using the RT-PCR method. In addition, theoretical analyzes were made. The IC50 values of docetaxel after 24, 48 and 72 h were 8.32 ±1.45 μg/ml, 7.67 ±2.56 μg/ml and 5.51 ±1.24 μg/ml, respectively. According to the results obtained, docetaxel was found to have the highest activity in 72 h of incubation. It was determined that the do- cetaxel drug decreased the expression level of the hTERT gene in SH-SY5Y cells. Telomere lengths were significantly reduced in the docetaxel treated SH-SY5Y cell line compared to the control group ( p < 0.05). Molecular docking analysis results were in agreement with the experiments. Analysis results indicated a good interaction between docetaxel and the active site of telomerase. The results of this study, reinforced by molecular docking analyzes, might be proved valuable for the development of potent telomerase in- hibitors.
0005-01-01T00:00:00ZIn vitro cytotoxic effects, in silico studies, some metabolic enzymes inhibition, and vibrational spectral analysis of novel β-amino alcohol compounds
https://hdl.handle.net/20.500.12418/14846
In vitro cytotoxic effects, in silico studies, some metabolic enzymes inhibition, and vibrational spectral analysis of novel β-amino alcohol compounds
Tas, Ayca; Tüzün,Burak; Khalilov, Ali N; Taslimi, Parham; Agbektas, Tugba; Keklikcioglu Cakmak, Nese
In this study, an efficient single-step method for the preparation of β-amino alcohols ( 1 –3 ) in aqueous
media was applied. The aim was to investigate the cytotoxic activity of Compounds 1, 2 and 3 in neu-
roblastoma SH-SY5Y cell line and mouse fibroblast l -929 cell lines. Cytotoxic activities of compounds
1, 2 and 3 in this cell lines were also determined by MTT method. Cells were incubated with differ-
ent concentrations of Compound 3 showed the highest cytotoxic activity in SHY5Y cells at an IC50 dose
of 13.01 ±0.87 μM at 72 h compared to other compounds. Compound 3 was determined to have lower
cytotoxic activity in l -929 cells. The chemical activities of the molecules against the B3LYP, HF, M062X
level 3–21 g, 6–31 g, and SDD basis set with the Gaussian package program and biologically against
the adenosine A(2A) receptor (PDB ID: 3PWH and 5NM4) proteins for neuroblastoma tumors cell with
the Maestro Molecular modeling platform by Schrödinger were compared. Both experimental and the-
oretical NMR, UV–vis, and IR spectra of the studied molecules were compared. ADME/T analysis was
performed to examine the drug properties of the molecules. Finally, these assayed for their activities
against metabolic enzymes acetylcholinesterase and α-glucosidase. The most potent compounds against
AChE were order compounds 3, 2 and 1 with K i values of 35.88 ±6.61, 43.75 ±8.28, and 45.34 ±3.50 μM
against AChE, respectively. The results indicated that all the synthesized compounds exhibited excellent
inhibitory activities against mentioned enzymes as compared with standard inhibitors. These inhibitors
may be candidates for drug design.
2023-01-01T00:00:00ZAnticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
https://hdl.handle.net/20.500.12418/14845
Anticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
Inandiklioglu, Nihal; Tas, Ayca; Agbektas, Tugba; Tuncbilek, Zuhal; Raheem, Yomi Kayode; Cinar, Gulcihan; Silig, Yavuz
Neuroblastoma is the most common extracranial solid tumor of infancy in a broad range of clinical
courses, ranging from spontaneous regression to fatal progression. Telomere maintenance plays an impor-
tant role in genome stability and cell proliferation. Telomerase reverse transcriptase (hTERT in humans) is
a catalytic subunit of the enzyme telomerase. In this study, it was aimed to determine the anticancer ac-
tivity of the docetaxel chemotherapeutic agent in neuroblastoma cell line (SH-SY5Y) and to investigate its
effect on hTERT gene expression level and telomere length. Molecular docking studies were performed on
docetaxel with the crystal structure of telomerase. The electronic properties of docetaxel were calculated
using the density functional theory (DFT) method. SH-SY5Y cells were treated for 24, 48 and 72 h with
specific concentrations of docetaxel drug ranging from 1 to 100 μg/ml. IC50 doses of docetaxel were de-
termined and administered to SH-SY5Y cells, followed by RNA isolation. hTERT and MYC gene expression
levels and telomere length were measured in the docetaxel-treated sample using the RT-PCR method.
In addition, theoretical analyzes were made. The IC50 values of docetaxel after 24, 48 and 72 h were
8.32 ±1.45 μg/ml, 7.67 ±2.56 μg/ml and 5.51 ±1.24 μg/ml, respectively. According to the results obtained,
docetaxel was found to have the highest activity in 72 h of incubation. It was determined that the do-
cetaxel drug decreased the expression level of the hTERT gene in SH-SY5Y cells. Telomere lengths were
significantly reduced in the docetaxel treated SH-SY5Y cell line compared to the control group ( p < 0.05).
Molecular docking analysis results were in agreement with the experiments. Analysis results indicated a
good interaction between docetaxel and the active site of telomerase. The results of this study, reinforced
by molecular docking analyzes, might be proved valuable for the development of potent telomerase in-
hibitors.
2023-01-01T00:00:00Z