葛根素衍生物的设计合成及其对酪氨酸酶的激活作用研究  

Design and Synthesis of Puerarin Derivatives and Their Activation Effects on Tyrosinase

作　　者：朱号天 宋科[1,2] 于华忠 贺健[1,2] 刘诗马 郭婕 ZHU Haotian;SONG Ke;YU Huazhong;HE Jian;LIU Shima;GUO Jie(Key Laboratory of Hunan Forest Product and Chemical Industry Engineering,Jishou University,Zhangjiajie 427000,China;College of Chemistry and Chemical Engineering,Jishou University,Jishou 416000,China)

机构地区：[1]吉首大学林产化工工程湖南省重点实验室,湖南张家界427000 [2]吉首大学化学化工学院,湖南吉首416000

出　　处：《林产化学与工业》2024年第4期61-69,共9页Chemistry and Industry of Forest Products

基　　金：国家自然科学基金资助项目(32060326)。

摘　　要：以葛根素为原料,设计合成8个葛根素衍生物(PD_(1)~PD_(8)),通过质谱和核磁共振氢谱确定其化学结构,利用酪氨酸酶多巴速率氧化法测定各衍生物对酪氨酸酶的激活活性,并利用分子对接模拟探讨各衍生物与酪氨酸酶的结合情况,酶动力学分析确定激活类型。8个葛根素衍生物结构鉴定为:4'-甲氧基-葛根素(PD_(1))、4'-乙氧基-葛根素(PD2)、4'-丙氧基-葛根素(PD3)、7-O-乙酰基-葛根素(PD4)、7-O-三甲基乙酰基-葛根素(PD5)、7-甲氧基-葛根素(PD6)、7-O-乙氧羰基亚甲基-葛根素(PD7)、7,4'-O-二乙氧羰基亚甲基-葛根素(PD_(8))。激活活性测定结果表明:PD6为混合型激活,PD6的半激活浓度EC50=0.416 mmol/L,高于葛根素(EC50=0.434 mmol/L)。Eight puerarin derivatives(PD_(1)-PD_(8))were designed and synthesized from puerarin,and their chemical structures were determined by mass spectrometry and nuclear magnetic resonance hydrogen spectroscopy.The activation activity of each derivative on tyrosinase was measured using the method of tyrosinase dopa rate oxidation.Molecular docking simulations were utilized to explore the binding mechanism of each derivative with tyrosinase.Enzyme kinetic analysis was performed to determine the type of activation.The structures of 8 puerarin derivatives were identified as:4-methoxy-puerarin(PD_(1)),4-ethoxy-puerarin(PD 2),4-propoxyl-puerarin(PD 3),7-O-acetyl-puerarin(PD 4),7-O-trimethylacetyl-puerarin(PD 5),7-methoxy-puerarin(PD 6),7-O-ethoxycarbonylmethylene-puerarin(PD 7),7,4-O-diethoxycarbonylmethylene-puerarin(PD_(8)).Enzyme kinetic results showed that PD 6 were mixed activation types.The results of activation activity assay showed that PD 6 was mixed activation,and the half activation concentration of PD 6(EC 50=0.416 mmol/L)was higher than that of puerarin(EC 50=0.434 mmol/L).

关 键 词：葛根素衍生物 合成 酪氨酸酶激活剂 动力学分析 

分 类 号：TQ35[化学工程]