Synthesis and anti-tyrosinase mechanism of the substituted vanillyl cinnamate analogues.
This study aimed to synthesize and screen tyrosinase inhibitors for delay fruit browning. A series of vanillyl cinnamate analogues were designed and synthesized by simple processes, and the inhibitory effects of all the synthesized derivatives on mushroom tyrosinase were evaluated. In the enzymatic activity test, compounds 21, 22, and 26 had significant (P < 0.05) effect on mushroom tyrosinase at a preliminary screening dose (1 mg/mL in vitro). IC50 analysis showed that the IC50 values of compounds 21, 22 and 26 were 268.5 μM, 213.2 μM and 413.5 μM, respectively. In the cytotoxicity evaluation, Cell Counting Kit-8 (CCK-8) assay showed that compounds 21, 22 and 26 had no significant effect on the proliferation of hepatocyte L02 and B16 melanoma cells at the dosage of 25-200 μM. Inhibition of tyrosinase activity and melanin content in B16 melanoma cells investigations indicated that compounds 21, 22 and 26 inhibited both cellular tyrosinase activity and melanin content dose-dependently and more strongly than the reference standard arbutin. The UV-visible spectra showed compound 22 inhibits the formation of dopamine quinone, further the molecular docking analysis of compound 22 with tyrosinase (PDB: 2Y9X) indicated that compound 22 interacted with the amino acid residues of tyrosinase. The results of anti-browning test showed that compounds 21, 22 and 26 had significant tyrosinase inhibition and anti-browning effects on fresh-cut apple slices at 4 °C in 48 h. Compound 22 could be used as novel tyrosinase inhibitor to delay fruit browning.
['Zhao|Zefeng|Z|', 'Liu|Guangxin|G|', 'Meng|Yufeng|Y|', 'Tian|Jiale|J|', 'Chen|Xufei|X|', 'Shen|Meilun|M|', 'Li|Yuexuan|Y|', 'Li|Bingyao|B|', 'Gao|Cong|C|', 'Wu|Shaoping|S|', 'Li|Cuiqin|C|', 'He|Xirui|X|', 'Jiang|Ru|R|', 'Qian|Mingcheng|M|', 'Zheng|Xiaohui|X|']
D000363:Agaricales D000818:Animals D001665:Binding Sites D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D002934:Cinnamates D004791:Enzyme Inhibitors D007700:Kinetics D008543:Melanins D051379:Mice D062105:Molecular Docking Simulation D014442:Monophenol Monooxygenase D017434:Protein Structure, Tertiary D013329:Structure-Activity Relationship
Tyrosinase Inhibitor Docking Cinnamic acid