The synthesis, characterization and molecular docking studies of novel Schiff bases bearing 1-(o-tolyl)-4-(phenoxymethyl)-(1H)1,2,3-triazole derivatives

Compounds including a triazole skeleton and an imine functional group in their structures have a broad range of applications in drug discovery due to their biological activities. Herein, the novel Schiff bases bearing 1-(o-tolyl)-4-(phenoxymethyl)-(1H)1,2,3-triazole derivatives were synthesized and the structures of newly synthesized compounds were characterized by FTIR, 1D and 2D NMR and mass spectral data. Computational analysis was performed to optimize the structures of the synthesized compounds with density functional theory (DFT) using the B3LYP method at the 6-311++G(d,p) basis set in the gas phase. The binding affinity values obtained from docking studies of Schiff bases (2a-2d) on sterol 14α-demethylase (CYP51) indicate that compounds 2c and 2d have a higher potential as CYP51 inhibitors compared to compounds 2a and 2b. It was found that the incorporation of a benzene ring into the structure significantly increased the binding affinity from -9.0 to -11.5 kcal mol-1.