In Silico and In Vitro Studies of Novel Azomethines on DNA Repair Genes in Gastric Cell Lines

We herein report the determination of the cytotoxic activity and expression profiles of some DNArepair 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 werecharacterized by 1Hand13CNMRspectroscopymethods. Furthermore, theywereappliedtothe AGScell line at eight different concentrations (0.1–50 g/mL). Anticancer activities were determined using the MTTmethod. Expressionlevels of ATR,ERCC1, TOP2A,andABCB1genesweredetermined by the RT-PCRmethod. 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 g/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