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

Abstract

The main aims of anticancer drug development studies is to reduce the toxicity of the developed com- pound 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 re- cent 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 path- way ( 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 path- way ( 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 can- cer 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.