新型基于羟基苯甲醛的曲酸类似物作为蘑菇酪氨酸酶抑制剂的合成及生物学评价
Synthesis and biological evaluation of novel hydroxybenzaldehyde-based kojic acid analogues as inhibitors of mushroom tyrosinase.
作者信息
Xie Wenlin, Zhang Huilin, He Jingjing, Zhang Jingai, Yu Qiuyan, Luo Chunxiang, Li Shangru
机构信息
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Organic Chemistry and Function Molecule of Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, China; Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Xiangtan 411201, China.
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China.
出版信息
Bioorg Med Chem Lett. 2017 Feb 1;27(3):530-532. doi: 10.1016/j.bmcl.2016.12.027. Epub 2016 Dec 9.
Two series of novel kojic acid analogues (4a-j) and (5a-d) were designed and synthesized, and their mushroom tyrosinase inhibitory activities was evaluated. The result indicated that all the synthesized derivatives exhibited excellent tyrosinase inhibitory properties having IC values in the range of 1.35±2.15-17.50±2.75μM, whereas standard inhibitor kojic acid have IC values 20.00±1.08μM. Specifically, 5-phenyl-3-[5-hydroxy-4-pyrone-2-yl-methylmercap-to]-4-(2,4-dihydroxyl-benzylamino)-1,2,4-triazole (4f) exhibited the most potent tyrosinase inhibitory activity with IC value of 1.35±2.15μM. The kinetic studies of the compound (4f) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure-activity relationship was discussed.
设计并合成了两个系列的新型曲酸类似物（4a-j）和（5a-d），并评估了它们对蘑菇酪氨酸酶的抑制活性。结果表明，所有合成衍生物均表现出优异的酪氨酸酶抑制特性，IC值在1.35±2.15-17.50±2.75μM范围内，而标准抑制剂曲酸的IC值为20.00±1.08μM。具体而言，5-苯基-3-[5-羟基-4-吡喃酮-2-基-甲基巯基]-4-(2,4-二羟基-苄基氨基)-1,2,4-三唑（4f）表现出最有效的酪氨酸酶抑制活性，IC值为1.35±2.15μM。对化合物（4f）的动力学研究表明，该化合物对酪氨酸酶的抑制作用属于竞争性抑制剂。同时，还讨论了构效关系。
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