Design, Synthesis, Biological Activity and Molecular Docking Studies of New Imine-Chalcone Derivatives

Schiff base derivatives, owing to their non-toxic qualities and biodegradability are widely used in the pharmaceutical-chemical industry, agriculture, and materials science. In this work, nine bioactive imine-chalcone derivatives were synthesized and their cytotoxic activities, inhibitory effects on tyrosinase, and molecular docking properties were evaluated. Cytotoxic effects of new compounds 12-20 were investigated by using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay on lung carcinoma (A549) cell line. To provide insights into their tyrosinase inhibiting mechanisms, molecular docking studies were performed. The results showed that almost all of the new compounds exhiibited weak growth inhibition at tested concentrations (0.125 – 250 μM). Compounds 13 , 16 , and 17 exhibited significant tyrosinase inhibition effects with the IC 50 values of 6.14 ± 0.50, 46.39 ± 1.32, and 61.58 ± 0.88 μM when compared to standard kojic acid (52.36 ± 1.05). According to molecular docking studies, compounds 13 , 16 , and 17 possess the excellent binding interest to tyrosinase (-8.13, -8.00, and -8.06 kcal/mol, respectively) comparing standard kojic acid (-3.96 kcal/mol). These results suggest that compounds 13 , 16 , and 17 are potent tyrosinase inhibitors.