Molecular docking studies and biological evaluation of 1,3,4-thiadiazole derivatives bearing Schiff base moieties as tyrosinase inhibitors

Compound 14 exhibited most potent tyrosinase inhibitory activity with IC50 value of 0.036μM. The inhibition kinetics study revealed that compounds (13, 14) exhibited such inhibitory effects on tyrosinase by acting as the uncompetitive inhibitors. Docking study was carried out. The LD50 value of the compound 14 was 5000mg/kg. [Display omitted] •New tyrosinase inhibitory was evaluated.•IC50 value of the most potent tyrosinase inhibitor is 0.036μM.•Compound 13 and compound 14 are uncompetitive inhibitors.•Docking study was carried out.•The LD50 value of the compound 14 was 5000mg/kg. 1,3,4-Thiadiazole derivatives bearing Schiff base moieties were designed, synthesized, and their tyrosinase inhibitory activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, 4-(((5-mercapto-1,3,4-thiadiazol-2-yl)-imino)methyl)-2-methoxy-phenol (14) exhibited superior inhibitory effect to the other compounds with an IC50 value of 0.036μM. The structure–activity relationships (SARs) were preliminarily discussed and docking studies showed compound 14 had strong binding affinity to mushroom tyrosinase. Hydroxy might be the active groups. The inhibition kinetics study revealed that compounds (13 and 14) inhibited tyrosinase by acting as uncompetitive inhibitors. The LD50 value of the compound 14 was 5000mg/kg.