蘑菇酪氨酸酶抑制剂的合成、生物活性与分子对接研究

Synthesis,Biological Evaluation,and Molecular Docking of Tyrosinase Inhibitors from Mushroom

合成并测试了6种苯甲醛缩胺基硫脲类衍生物对蘑菇酪氨酸酶的抑制活性。结果表明,苯环2位羟基对酶抑制活性起到关键作用。化合物1a(R=2-OH)和1b(R=2-OH-4-OCH3)对单氧化酶的IC_(50)值分别为(0.65±0.09)μM和(0.46±0.04)μM,对双氧化酶的IC50值分别为(5.15±0.17)μM和(3.31±0.10)μM。分子对接表明化合物1a的硫原子与铜离子形成配位作用,亚胺氮原子与His85和His259形成两个氢键,同时,分子内氢键作用对提升疏水作用也具有一定的帮助。

Six benzaldehyde thiosemicarbazones were synthesized and evaluated their mushroom tyrosinase inhibition activity.The results showed compounds 1a(R=2-OH)and 1b(R=2-OH-4-OCH3)exhibited the IC50 values of 0.65±0.09μM and 0.46±0.04μM against monooxidase,5.15±0.17μM and 3.31±0.10μM against dioxidase,respectively,which means the 2-position of benzene ring plays an important role in the activity.Molecular docking results showed the sulfur atom of 1a can chelate with Cu2+,and imine formed two hydrogen bonds with His85 and His259,further,the hydrophobic can be increased because of the intramolecular hydrogen bond.