Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors

Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very important in medicine, cosmetics and agriculture. In order to develop more active and safer tyrosinase inhibitors, an efficient approach is to mod...

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Published in:MedChemComm 2018, Vol.9 (5), p.853-861
Main Authors: Sheng, Zhaojun, Ge, Siyuan, Xu, Ximing, Zhang, Yan, Wu, Panpan, Zhang, Kun, Xu, Xuetao, Li, Chen, Zhao, Denggao, Tang, Xiaowen
Format: Article
Language:English
Subjects:
Agricultural development
Biosynthesis
Cinnamic acid
Cosmetics
Derivatives
Docking
Enzymic browning
Esterification
Food plants
Inhibition
Inhibitors
Kinetics
Kojic acid
Medicinal plants
Melanin
Plants
Thymol
Tyrosinase
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Summary:Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very important in medicine, cosmetics and agriculture. In order to develop more active and safer tyrosinase inhibitors, an efficient approach is to modify natural product scaffolds. In this work, two series of novel tyrosinase inhibitors were designed and synthesized by the esterification of cinnamic acid derivatives with paeonol or thymol. Their inhibitory effects on mushroom tyrosinase were evaluated. Most of these compounds (IC : 2.0 to 163.8 μM) are found to be better inhibitors than their parent compounds (IC : 121.4 to 5925.0 μM). Among them, ( )-2-acetyl-5-methoxyphenyl-3-(4-hydroxyphenyl)acrylate ( ), ( )-2-acetyl-5-methoxyphenyl-3-(4-methoxyphenyl)acrylate ( ) and ( )-2-isopropyl-5-methylphenyl-3-(4-hydroxyphenyl)acrylate ( ) showed strong inhibitory activities; the IC values were 2.0 μM, 8.3 μM and 10.6 μM, respectively, compared to the positive control, kojic acid (IC : 32.2 μM). Analysis of the inhibition mechanism of , and demonstrated that their inhibitory effects on tyrosinase are reversible. The inhibition kinetics, analyzed by Lineweaver-Burk plots, revealed that acts as a non-competitive inhibitor while and are mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between and mushroom tyrosinase.
ISSN:2040-2503
2040-2511
DOI:10.1039/c8md00099a