曲酸三氮唑氨基硫脲席夫碱的合成及抑制酪氨酸酶活性研究  

Study on the synthesis and tyrosinase inhibition activity of kojic acid triazol thiosemicarbazide Schiff base derivatives

作　　者：罗亚园 刘进兵 LUO Ya-yuan;LIU Jin-bing(Department of Food and Chemical Engineering,Shaoyang University,Shaoyang 422000,China)

机构地区：[1]邵阳学院食品与化学工程学院,湖南邵阳422000

出　　处：《化学研究与应用》2024年第3期556-564,共9页Chemical Research and Application

基　　金：湖南省自然科学基金项目(2022JJ50189)资助;湖南省教育厅重点项目(22A0536)资助;邵阳学院研究生科研创新项目(CX2022SY074)资助。

摘　　要：本研究基于蘑菇酪氨酸酶晶体结构特点,设计并合成了11个曲酸三氮唑氨基硫脲席夫碱衍生物。抑制酪氨酸酶活性研究发现,所有化合物均能一定程度抑制酪氨酸酶活性,其中化合物7j抑制效果最好,其IC_(50)为1.584μM,优于阳性对照曲酸(IC_(50)为22.230μM);作用机制研究表明,该化合物为混合型抑制剂,不仅能与游离酶结合,还能与酶-底物复合物相结合,其K_(I)和K_(IS)分别为0.059 3μM和0.100 6μM;进一步的荧光猝灭和实际抗褐变结果表明该化合物不仅对酪氨酸酶有很好的动态猝灭作用,其实际抗褐变效果也优于曲酸和抗坏血酸;上述研究结果为开发安全、高效的酪氨酸酶抑制剂提供了理论依据。In this study,the synthesis,tyrosinase inhibitory activities and anti-browning effects of kojic acid triazol thiosemicarbazide Schiff base derivatives were reported.Mushroom tyrosinase inhibitory assay showed that all of the compounds exhibited potent inhibitory activities.Compound 7j possessed the most potent tyrosinase inhibitory activity with the IC_(50) values of 1.584 μM,and showed better inhibitory activity than the positive control kojic acid(IC_(50)=22.230 μM).Inhibition mechanism indicated that compound 7j was a mixed-type inhibitor,and could bind to both free enzyme and enzyme-substrate complex.K_(I) and K_(IS) values of the compound 7j were 0.059 3 μM and 0.100 6 μM,respectively.In addition,fluorescence quenching result demonstrated that compound 7j had excellent dynamic quenching effect on tyrosinase.Anti-browning evaluation exhibited compound 7j showed better anti-browning effect than kojic acid and ascorbic acid.These findings provided theory basis for the development of safe and efficient tyrosinase inhibitors.

关 键 词：曲酸衍生物 生物活性 酪氨酸酶抑制机理 抗褐变 

分 类 号：O657[理学—分析化学]