Chalcone-based schiff bases: Design, synthesis, structural characterization and biological effects

Abstract

The presented work describes the synthesis, characterization, and biological effects of three new Schiff base compounds (SOH-F/Cl/Br) and their phthalonitrile derivatives (SCN-F/Cl/Br). The structures of all synthesized compounds were elucidated by NMR, FT-IR, and mass spectroscopic methods. Enzyme results were obtained at the nanomolar level. Cytotoxic activity of novel compounds was evaluated against neuroblastoma (SH-SY5Y) and mouse fibroblast (NIH-3T3) cell lines using MTT. It has been determined that all tested molecules have a powerful cytotoxic effect; IC50 values were under 10 mu M against SH-SY5Y cells. Among all compounds, the lowest IC50 value was observed in SCN-Br (1.798 +/- 0.036 mu M). Moreover, the IC50 concentration of SCN-Br (12.79 +/- 0.33 mu M) in healthy NIH-3T3 cells was significantly higher than in cancerous cells. The activity comparison of the studied six molecules was made with both DFT calculations and molecular docking calculations. Various proteins that are hCA I protein (PDB ID: 2CAB), hCA II protein (PDB ID: 5AML), and SH-SY5Y protein (PDB ID: 7LQZ, 5WIV, and 2F37) were used in molecular docking calculations. After this comparison, ADME/T calculations were used to analyze the molecules to be used as drugs.