Molecular docking studies and biological evaluation of 1,3,4-thiadiazole derivatives bearing Schiff base moieties as tyrosinase inhibitors.
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 IC50value 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 LD50value of the compound 14 was 5000mg/kg.
Department of Biology and Chemical Engineering, Shaoyang University, Shao Shui Xi Road, Shaoyang 422100, PR China.
Junyuan
J
Tang
Department of Biology and Chemical Engineering, Shaoyang University, Shao Shui Xi Road, Shaoyang 422100, PR China. Electronic address: syuliujb@163.com.
Jinbing
J
Liu
Department of Biology and Chemical Engineering, Shaoyang University, Shao Shui Xi Road, Shaoyang 422100, PR China.
Fengyan
F
Wu
D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D012545:Schiff Bases; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; D014442:Monophenol Monooxygenase
1,3,4-Thiadiazole derivatives; Docking studies; Inhibition kinetics; Tyrosinase inhibitory activities