In Silico and In Vitro Studies of Novel Azomethines on DNA Repair Genes in Gastric Cell Lines
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Date
28.09.2023Author
Ozturk, AlpaslanAgbektas, Tugba
Huseynzada, Alakbar
Guliyev, Ruslan
Ganbarova, Rana
Hasanova, Ulviyya
Tas, Ayca
Erkan, Sultan
Zontul, Cemile
Inandiklioglu, Nihal
Silig, Yavuz
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Show full item recordAbstract
We herein report the determination of the cytotoxic activity and expression profiles of
some DNA repair genes of newly synthesized azomethines in the gastric cancer cell line (AGS). The
studied novel compounds were synthesized by a condensation reaction and received compounds
were characterized by 1H and 13C NMR spectroscopy methods. Furthermore, they were applied to the
AGS cell line at eight different concentrations (0.1–50 µg/mL). Anticancer activities were determined
using the MTT method. Expression levels of ATR, ERCC1, TOP2A, and ABCB1 genes were determined
by the RT-PCR method. Biochemical parameters were also examined. The interaction of proteins with
other proteins was investigated with the String v11 program. The IC50 values of compounds 1, 2, and
3 obtained after 72 h were 23.10, 8.93, and 1.58 µg/mL, respectively. The results demonstrate that the
cytotoxic activity of compound 3 on AGS cancer cells is higher in comparison with other molecules.
It was determined that the expression levels of ATR, TOP2A, and ABCB1 genes in compounds 1, 2,
and 3 were decreased compared to the control group. In addition, it was determined that ERCC1
gene expression increased in compound 3, decreased in compound 2, and remained unchanged in
compound 1 (p < 0.001). In AGS gastric cancer cells, a 64% decrease was detected for GST levels in
compound 1, while a 38% decrease in GSH levels in compound 2. In addition, compounds 1–3 were
examined at the molecular level with computational techniques and the docking studies revealed
4LN0 as a target protein.